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Protein
& Peptide Letters
ISSN: 0929-8665
Protein &
Peptide Letters
Volume 16, Number 5, 2009
Contents
Proteome/Protein/Peptide in Molecular Medicine
Guest Editor: John M. Luk
Editorial
Pp. 457-459
J.M. Luk
[PMID:
19442222 PubMed - indexed for MEDLINE]
Metabolomics of Serum Peptides Pp. 460-466
R. Doshi and P.J.R. Day
[Abstract] [Purchase
Article] [PMID:
19442223 PubMed - indexed for MEDLINE]
SELDI Protein Chip Technology for the
Detection of Serum Biomarkers for Liver Disease Pp.
467-472
L. Chen, S. Fatima, J. Peng and
X. Leng
[Abstract] [Purchase
Article] [PMID:
19442224 PubMed - indexed for MEDLINE]
Biomarkers for Early Detection of Liver
Cancer: Focus on Clinical Evaluation Pp. 473-478
S. Sun, P.J.R. Day, N.P. Lee and
J.M. Luk
[Abstract] [Purchase
Article] [PMID:
19442225 PubMed - indexed for MEDLINE]
Proteomic Identification of a Monoclonal
Antibody Recognizing Caveolin-1 in Hepatocellular Carcinoma
with Metastatic Potential Pp. 479-485
M.-y. Hu, C.-t. Lam, K.-d. Liu, Z. Xu,
S. Fatima, Y.C.F Su, F. Tsang, J. Chen, J.-z. Pang, L.-x.
Qin and J.M. Luk
[Abstract] [Purchase
Article] [PMID:
19442226 PubMed - indexed for MEDLINE]
PSMA7, A Potential Biomarker of Diseases
Pp. 486-489
H. Du, X. Huang, S. Wang, Y. Wu, W.
Xu and M. Li
[Abstract] [Purchase
Article] [PMID:
19442227 PubMed - indexed for MEDLINE]
Chitinases: Biomarkers for Human Diseases
Pp. 490-498
S.-P. Guan, Y.-K. Mok, K.-N. Koo, K.-L.
Chu and W.S.F. Wong
[Abstract] [Purchase
Article] [PMID:
19442228 PubMed - indexed for MEDLINE]
Implication of Aberrant Glycosylation
in Cancer and Use of Lectin for Cancer Biomarker Discovery
Pp. 499-507
Y.-S. Kim, H.S. Yoo and J.H.
Ko
[Abstract] [Purchase
Article] [PMID:
19442229 PubMed - indexed for MEDLINE]
Heat Shock Proteins in Cancer: Signaling
Pathways, Tumor Markers and Molecular Targets in Liver Malignancy
Pp. 508-516
W.J. Lu, N.P. Lee, S. Fatima and
J.M. Luk
[Abstract] [Purchase
Article] [PMID:
19442230 PubMed - indexed for MEDLINE]
The Versatile Stress Protein Mortalin
as a Chaperone Therapeutic Agent Pp. 517-529
C.C. Deocaris, S.C. Kaul and
R. Wadhwa
[Abstract] [Purchase
Article] [PMID:
19442231 PubMed - indexed for MEDLINE]
The Use of Small Peptides in the Diagnosis and
Treatment of Hepatocellular Carcinoma Pp. 530-538
F.H. Tsang, N.P. Lee and J.M.
Luk
[Abstract] [Purchase
Article] [PMID:
19442232 PubMed - indexed for MEDLINE]
Endotoxin-Neutralizing Peptides as Gram-Negative
Sepsis Therapeutics Pp. 539-542
K.-F. Wong and J.M. Luk
[Abstract] [Purchase
Article] [PMID:
19442233 PubMed - indexed for MEDLINE]
General Articles
Regular Papers
Discovery of Novel Plant Peptides as Strong Inhibitors
of Metalloproteinases Pp. 543-551
D.M. Carrilho, I.C. Duarte, R. Francisco,
C.P.P. Ricardo and
M.C. Duque-Magalhães
[Abstract] [Purchase
Article] [PMID:
19442234 PubMed - indexed for MEDLINE]
Using Maximum Entropy Model to Predict
Protein Secondary Structure with Single Sequence Pp.
552-560
Y.-S. Ding, T.-L. Zhang, Q. Gu, P.-Y.
Zhao and K.-C. Chou
[Abstract] [Purchase
Article] [PMID:
19442235 PubMed - indexed for MEDLINE]
Estimation of Affinity of HLA-A*0201
Restricted CTL Epitope Based on the SCORE Function Pp.
561--569
L. Zhi-Hua, W. Huai-Liang, Z. Bo, W.
Yuan-Qiang, L. Yong and W. Yu-Zhang
[Abstract] [Purchase
Article] [PMID:
19442236 PubMed - indexed for MEDLINE]
Abstracts
[Back to top]
[PMID:
19442222 PubMed - indexed for MEDLINE]
Editorial: The
“3Ps” World – From Disease Markers to Biological
Therapeutics
This special hot-topic issue focuses on 3 “P”
words – Proteome, Protein and Peptide, in this fast-discovering
field of molecular medicine. Indeed, the volume of indexed
publications and relevant successfully filed patents could
reflect the importance of the “3Ps” in this topic
(see Table 1). The major scope herein is
to highlight some novel and innovative molecular and cellular
approaches in these “3Ps” for identification of
disease biomarkers as diagnostics and development of potential
biological therapeutics for the treatment of diseases like
cancer and immunological disorders.
In the year 2000, the completion of human genome sequence
has brought forth a new set of challenges for advancing science
and technology. In particular, the emergence of genomics,
proteomics, and bioinformatics has allowed us to systematically
analyze large amount of sequence information and expression
profiling data and studying biological systems on a global
level. In this context, research on genomics and proteomics
can help speed up the drug development process, taking a foothold
in every stage of the drug discovery process and in clinical
practice, ranging from drug target identification and validation,
biomarker discovery and pharmacokinetics/pharmacodynamics
analysis to toxicological studies. Among these disciplines,
it becomes increasingly apparent that the proteomics will
have a major role in creating a predictive, preventative,
and personalized approach to medicine. Proteomics-based approaches
have dominated the field, but still have faced many challenges
due to technological limitations and biological complexity
that were not expected before; more precisely, the detection
limit of low-abundance proteins in plasma or sera and the
presence of vast numbers of post-translational modified isoforms
[1].
As such, there is still an urgent need for novel strategies
and technologies. Despite these challenges, the impact of
proteomics will be far-reaching, and significant progress
has already been made. Moving forward, the issue of how to
use proteomics tools, proteins and peptides as markers and
therapeutics to improve the health of individuals must be
a priority.
FROM PROTEOMICS, PEPTIDOMICS TO METABOLOMICS
Proteomics is the study of protein expression, structure and
function. However, the area of metabolomics – the study
of metabolites and analytes are understudied. Doshi and Day
[2] advocated the Tripod theory about “Cause, Effect
and Therapeutic Intervention”. Take cancer as an example,
the growing pressure and increasing hypoxia conditions in
tumor site would cause the tumor leaky microvasculature and
the release of tumor-specific peptide biomarkers or tumor-conditioned
metabolites into the vascular system. In this context, the
SELDI-ToF ProteinChip technology has been invented for monitoring
the serum profile changes from healthy to diseased states.
L. Chen et al. [3] has revealed one good example
using the SELDI-ToF technology to profile protein fingerprint
peptides between healthy subjects and patients from chronic
hepatitis, NASH, cirrhosis to liver malignancies. Identification
of protein markers can be done on chip digestion followed
by MALDI-ToF MS or C-terminal sequencing.
To improve the reproducibility and error-free peptide quantification,
microfluidic device that innately reduces the time-lag between
blood sampling and serum extraction would minimize proteomic/peptidomic
secretions from blood cells ex-vivo and enable multiplexing
of sample preparation and MALDI analysis. Peptides are of
a lower toxicity in nature, and could be used as drugs or
in drug delivery systems.
BIOMARKERS AND RELATED TECHNOLOGIES
The search for disease biomarkers has promised to reduce mortality
by enabling detection and subsequent intervention at earlier,
more treatable stages of the disease. Despite the plethora
of candidate biomarkers discovery so far, S. Sun et al.
[4] commented that blood/serum peptidomics in disease diagnosis
and therapy is still in its infancy. Before this novel class
of diagnostic analytes can be released for routine clinical
utility, the biomarker usage for diagnosis, prognosis and
prediction has to be rigorously validated by using more than
one method, and we should focus on clinical evaluation of
both diagnostic and prognostic biomarkers for defined disease
conditions. The National Cancer Institute of the National
Institute of Health has launched a 5-step model for clinical
validation of biomarkers prior to clinical uses.
Protease and ubiquitination-proteasome are involved in a diverse
physiological process regulating cell proliferation or cell
cycle control, transcriptional regulation, immune and stress
response, cell differentiation, and apoptosis. Because of
its frequent dysregulation in various types of disease, the
PSMA7 subunit of the 20S proteasome core complex has been
suggested as a potential disease marker and molecular target
[5]. It plays a pivotal role in response to hypoxia, stress
and hepatitis conditions, by regulating the HIF-α
and AP-1 degradation as well as endocytic trafficking.
The cell cycle and viral replication activities are thus affected.
Although humans do not produce chitin, we are constantly exposed
to chitin-containing organisms like insects and crustaceans.
There are a handful of chitinases and chitolectins identified
in humans and Fred Wong’s group [6] as the pioneer reviewed
the link of YKL-39 autoantibodies to osteoarthritic diseases
and YLK-40 as biomarkers to patients with endotoxemia, rheumatoid
arthritis, osteoarthritis and various type of cancers including
breast, colon/rectum, ovary, lung, prostate, glioblastoma,
and melanoma.YKL-40 is also a potential prognostic marker
for the survival rate of cancer patients.
Post-translational protein modifications (PTM) have remained
a major area of research in cellular biochemistry and oncology.
There are still many unresolved questions and new protein
isoforms are increasingly identified. In this issue, J.H.
Ko’s group [7] has identified L-PHA as a useful disease
marker and that an increase in β1,6-branching
on N-linked glycans is associated with the metastatic potential
of cancer cells. Other important glycoproteins include E-selectin,
LCA, Galectins, and E-PHA in immune disorders and cancers.
Likewise, M.Y. Hu et al. has discovered a novel isoform
of caveolin that is unique in hepatoma cells associated with
high metastatic potential [8]. They used the proteomics-based
MS approach to characterize the antigenic specificity of a
monoclonal antibody recognizing this caveolin isoform in invasive
cancer cell type. Monoclonal antibody has long been an essential
tool for target identification and validation and diagnostics
technology, and recently, has come under the spotlight for
biological therapeutics in oncology and immunity [9].
Heat shock proteins are a superfamily of chaperones, which
play key roles in cell survival and stress responses. Malignant
tumors are often under “stress” – hypoxia
and glucose deprivation. In order to survive and to gain protection
from proapoptotic stimuli, tumor cells usually upregulate
a vast number of heat shock proteins and cognate endoplasmic
reticulum (ER)-stress glucose-regulated proteins (GRPs) [10].
Targeting the heat shock protein family members has drawn
intense interest in drug development against cancers [11].
PEPTIDES AS DIAGNOSTICS, DRUG DELIVERY AND THERAPEUTICS
As mentioned above, peptides or peptide fingerprint signatures
are unique biomarkers for monitoring disease progression or
surveillance. More interestingly, the discovery of cell-penetrating
peptides, and the peptide-based delivery systems which can
cross cell membranes, makes certain peptides as an appealing
agent in drug discovery and pharmacokinetics/ pharmacodynamics
development. Tsang et al. gave a succinct overview
on the use of small peptides in the diagnosis and treatment
of hepatocellular carcinoma [12]. In nature, there are peptide
sequences known to bind and/or neutralize microbial toxins.
K.F. Wong [13] summarized the endotoxin-neutralizing peptides
and their potential uses in curing the life-threatening disease
sepsis.
As shown in the Table 1, the figures may
give us some hints about the biological importance and significant
impact of the proteome, proteins and peptides in biomedical
science. While the dollars sign heavily loads to the therapeutic
antibodies or proteins, the topic of metabolomics is apparently
understudied, and clinical validation of candidate biomarkers
seems to be at our top priority for translating our laboratory
discovery into clinical usages at the bedside.
Table 1. Number of Indexed Publications and Patents
in the Topics of Proteome, Proteins and Peptides in Molecular
Medicine as Biomarkers and Therapeutics
 Source:
ISI Web of Science (Edition, 2007)
REFERENCES
[1] Lee, N. P.; Cheung, S. T.; Poon, R. T.; Fan,
S. T.; Luk, J. M. Biomarkers Med., 2007,
1, 273-284.
[2] Doshi, R.; Day, P. J. Protein Pept. Lett., 2009,
16, 460-466.
[3] Chen, L.; Fatima, S.; Peng, J.; Leng, X. Protein Pept.
Lett., 2009, 16, 467-472.
[4] Sun, S.; Day, P. J.; Lee, N. P.; Luk, J. M. Protein
Pept. Lett., 2009, 16, 473-478.
[5] Du, H.; Huang, X.; Wang, S.; Wu, Y.; Xu, W.; Li, M.
Protein Pept. Lett., 2009, 16,
486-489.
[6] Guan, S. P.; Mok, Y. K.; Koo, K. N.; Chu, K. L.; Wong,
W. S. Protein Pept. Lett., 2009,
16, 490-498.
[7] Kim, Y. S.; Yoo, H. S.; Ko, J. H. Protein Pept. Lett.,
2009, 16, 499-507.
[8] Hu, M. Y.; Lam, C. T.; Liu, K. D.; Xu, Z.; Fatima, S.;
Su, Y. C.; Tsang, F. H.; Chen, J.; Pang, J. Z.; Qin, L. X.;
Luk, J. M. Protein Pept. Lett., 2009,
16, 478-485.
[9] Luk, J.M.; Wong, K.F. Clin. Exp. Pharmacol. Physiol.,
2006, 33, 482-488.
[10] Lu, W. J.; Lee, N. P.; Fatima, S.; Luk, J. M. Protein
Pept. Lett., 2009, 16, 508-516.
[11] Deocaris, C. C.; Kaul, S. C.; Wadhwa, R. Protein
Pept. Lett., 2009, 16, 517-529.
[12] Tsang, F. H.; Lee, N. P.; Luk, J. M. Protein Pept
Lett, 2009, 16, 530-538.
[13] Wong, K. F.; Luk, J. M. Protein Pept. Lett.,
2009, 16, 539-542.
John M. Luk
Guest Editor
Protein & Peptide Letters
Department of Surgery and Center for Cancer Research
The University of Hong Kong
Pokfulam
Hong Kong
[Back to top]
[Purchase
Article] [PMID:
19442223 PubMed - indexed for MEDLINE]
Metabolomics of Serum Peptides
R. Doshi and P.J.R. Day
Diseased-cell secreted proteins/peptides offer several
leads in biomarker development. Blood is a rich and universal
source of biomarkers because of its proximity to all cells
in the body. However, important physiological and practical
aspects need consideration before serum peptidomics is effectively
applied in a clinical, and later bedside, setting.
[Back to top]
[Purchase
Article] [PMID:
19442224 PubMed - indexed for MEDLINE]
SELDI Protein Chip Technology for the Detection of
Serum Biomarkers for Liver Disease
L. Chen, S. Fatima, J. Peng and
X. Leng
The need to identify disease biomarkers is critical to
ensure fast diagnosis and timely treatment. Surface enhanced
laser desorption/ionization time-of-fight mass spectrometry
(SELDI-TOF-MS) is a widely used technology platform for diagnostic
biomarker discovery. This short review provides an overview
of how it functions and also describes its advantages and
drawbacks.
[Back to top]
[Purchase
Article] [PMID:
19442225 PubMed - indexed for MEDLINE]
Biomarkers for Early Detection of Liver Cancer: Focus
on Clinical Evaluation
S. Sun, P.J.R. Day, N.P. Lee and J.M.
Luk
This review summarises the screening methods from hepatic
ultrasonography to serological biomarkers for early detection
of liver cancer and focuses on evaluation of biomarkers ability.
The development of novel biomarkers according to the 5-phase
program defined by the Early Detection Research Network (EDRN)
is also outlined in this review.
[Back to top]
[Purchase
Article] [PMID:
19442226 PubMed - indexed for MEDLINE]
Proteomic Identification of a Monoclonal Antibody
Recognizing Caveolin-1 in Hepatocellular Carcinoma with Metastatic
Potential
M.-y. Hu, C.-t. Lam, K.-d. Liu, Z. Xu, S.
Fatima, Y.C.F Su, F. Tsang, J. Chen, J.-z. Pang, L.-x. Qin
and J.M. Luk
A monoclonal antibody, McAb9E (IgG3), was generated against
a metastatic HCC cell line, MHCC-1. The antigen was characterized
as human Caveolin-1 (Cav-1, 21kDa), with pI of 5.65. The Cav-1
antigen was found significantly over expressed in metastatic
HCC cell lines as well as in tumor specimens. The Cav-1 specific
McAb may be a useful molecular agent for metastatic HCC.
[Back to top]
[Purchase
Article] [PMID:
19442227 PubMed - indexed for MEDLINE]
PSMA7, A Potential Biomarker of Diseases
H. Du, X. Huang, S. Wang, Y. Wu, W. Xu and
M. Li
Proteasome subunit alpha type 7(PSMA7) is an α-type
subunit of the 20S proteasome core complex and participates
in degrading proteins through ubiquitin-proteasome pathway
(UPP) which plays an important role in the regulation of cell
proliferation or cell cycle control, transcriptional regulation,
immune and stress response, cell differentiation, and apoptosis.
Previous studies have demonstrated that PSMA7 can be a target
interacting with some important proteins involved in transcription
factor regulation, cell cycle transition, viral replication
and even tumor initiation and progression, suggesting that
PSMA7 could be a potential target for the development of clinical
diagnosis and new therapeutic drugs. Here, we review the recent
studies on PSMA7 involved in many different cellular processes,
ranging from the cell cycle process to antigen processing
and tumorigenesis.
[Back to top]
[Purchase
Article] [PMID:
19442228 PubMed - indexed for MEDLINE]
Chitinases: Biomarkers for Human Diseases
S.-P. Guan, Y.-K. Mok, K.-N. Koo, K.-L. Chu
and W.S.F. Wong
Human chitinases (EC.3.2.1.14) are classified into family
18 of glycosyl hydrolase (GH18) superfamily based on their
amino acid sequence similarities. Active chitinase hydrolyzes
chitin, a β-1,4-linked
N-acetyl-D-glucosamine oligosaccharide. Chitin is
a major structural component of the insect exoskeletons and
fungal cell walls, but is not found in vertebrates. In human,
eight GH18 chitinases have been identified including active
chitotriosidase and acidic mammalian chitinase. Most of the
human chitinases lack chitinolytic activity due to mutation
of an essential glutamic acid residue at the catalytic domain,
and they are termed chitolectin. This review highlights some
characteristics of human chitinases, compares structural differences
among some human GH18 members, and discusses their cellular
regulation and function. Finally, we summarize current views
on the role of human chitinases in a variety of human diseases.
[Back to top]
[Purchase
Article] [PMID:
19442229 PubMed - indexed for MEDLINE]
Implication of Aberrant Glycosylation in Cancer and
Use of Lectin for Cancer Biomarker Discovery
Y.-S. Kim, H.S. Yoo and J.H. Ko
Aberrant glycosylation is frequently found in cancer,
and efforts for biomarker discovery include the preparation
of aberrant glycoproteins as promising analytes. Several lectins
that bind to aberrant glycans and can be thus used to capture
and enrich aberrant glycoproteins in the frontal stage during
biomarker discovery are to be introduced.
[Back to top]
[Purchase
Article] [PMID:
19442230 PubMed - indexed for MEDLINE]
Heat Shock Proteins in Cancer: Signaling Pathways,
Tumor Markers and Molecular Targets in Liver Malignancy
W.J. Lu, N.P. Lee, S. Fatima and J.M.
Luk
Heat shock proteins (HSPs) consist of a large group of
proteins with negligible expressions under physiological conditions.
Their expressions are highly induced under stress conditions
and they are ubiquitously expressed in various tissues and
organs. HSPs possess chaperone functions, thus facilitating
the correct folding of proteins or peptides. In hepatocellular
carcinoma (HCC), high expressions of HSPs are demonstrated
in liver cancer tissues and are correlated clinically with
the severity of tumors and poor outcomes of HCC patients.
This property enables them to be used as diagnostic markers
for the onset of HCC. Since their expressions are highly expressed
in liver cancer conditions, inhibitors or antisense oligonucleotides
of HSPs are postulated to serve as potential therapeutics
in treating this liver malignancy. In this review, we will
first introduce the HSP family and discuss the major signaling
pathways involved for the activities of HSPs. In addition,
the clinical applications of HSPs in liver cancer in the aspects
of diagnosis and therapy will be summarized and discussed.
[Back to top]
[Purchase
Article] [PMID:
19442231 PubMed - indexed for MEDLINE]
The Versatile Stress Protein Mortalin as a Chaperone
Therapeutic Agent
C.C. Deocaris, S.C. Kaul and R.
Wadhwa
Age- and stress-induced modulations in chaperone systems
result in “chaperono-deficiency” or “chaperonopulence”.
Development of modulators, of chaperone function has therefore,
become an emerging field in drug development and discovery.
This mini-review summarizes (i) the events leading to identification
of an Hsp70 family stress chaperone, mortalin, (ii) experimental
evidence to its role in old age diseases and cancer, and (iii)
proposes it as a chaperono-therapeutic agent. As post-translational
modifications and expression changes in mortalin are being
explored as a biomarker for cancer, cardiovascular diseases
and neurodegeneration, we discuss here how the current tools
used in studying mortalin (e.g. antibodies, peptides,
ribozymes, antisense and siRNA, recombinant proteins and small
molecules etc.) could be creatively applied in a clinical
setting to manage stress and to treat various chaperone-based
maladies or “chaperonopathies”.
[Back to top]
[Purchase
Article] [PMID:
19442232 PubMed - indexed for MEDLINE]
The Use of Small Peptides in the Diagnosis and
Treatment of Hepatocellular Carcinoma
F.H. Tsang, N.P. Lee and J.M. Luk
Hepatocellular carcinoma (HCC) is a malignant tumor unresponsive
to most current therapies. Small peptides, either synthetic
or derived from natural proteins, are found promising in treating
HCC. Herein, different types of small peptides and their associated
mechanistic actions against tumors are discussed, postulating
their use as alternative treatments for HCC.
[Back to top]
[Purchase
Article] [PMID:
19442233 PubMed - indexed for MEDLINE]
Endotoxin-Neutralizing Peptides as Gram-Negative
Sepsis Therapeutics
K.-F. Wong and J.M. Luk
Bacterial endotoxin [e.g. lipopolysaccharide (LPS)] can
trigger systemic hyper-inflammatory that subsequently leads
to multiple organ failure and lethality (gram-negative sepsis).
This paper describes the development of endotoxinneutralizing
peptides that potentially treat sepsis. These peptides have
been derived from bactericidal/permeability-increasing protein
(BPIP), anti-microbial peptides, and leukocyte CD18 antigen
and some of these peptides have been tested in clinical studies.
[Back to top]
[Purchase
Article] [PMID:
19442234 PubMed - indexed for MEDLINE]
Discovery of Novel Plant Peptides as Strong Inhibitors
of Metalloproteinases
D.M. Carrilho, I.C. Duarte, R. Francisco,
C.P.P. Ricardo and
M.C. Duque-Magalhães
Five novel metalloproteinase protein inhibitors (MPIs)
with molecular mass between 5.6 and 8.9 kDa and acid/neutral
pI were detected in lupin seeds and exhibited strong inhibitory
activities against thermolysin and/or gelatinase B. These
novel peptides constitute not only the first MPIs described
in plants but also the first plant peptides with inhibitory
activity against a matrixin.
[Back to top]
[Purchase
Article] [PMID:
19442235 PubMed - indexed for MEDLINE]
Using Maximum Entropy Model to Predict Protein Secondary
Structure with Single Sequence
Y.-S. Ding, T.-L. Zhang, Q. Gu, P.-Y. Zhao
and K.-C. Chou
Prediction of protein secondary structure is somewhat
reminiscent of the efforts by many previous investigators
but yet still worthy of revisiting it owing to its importance
in protein science. Several studies indicate that the knowledge
of protein structural classes can provide useful information
towards the determination of protein secondary structure.
Particularly, the performance of prediction algorithms developed
recently have been improved rapidly by incorporating homologous
multiple sequences alignment information. Unfortunately, this
kind of information is not available for a significant amount
of proteins. In view of this, it is necessary to develop the
method based on the query protein sequence alone, the so-called
single-sequence method. Here, we propose a novel single-sequence
approach which is featured by that various kinds of contextual
information are taken into account, and that a maximum entropy
model classifier is used as the prediction engine. As a demonstration,
cross-validation tests have been performed by the new method
on datasets containing proteins from different structural
classes, and the results thus obtained are quite promising,
indicating that the new method may become an useful tool in
protein science or at least play a complementary role to the
existing protein secondary structure prediction methods.
[Back to top]
[Purchase
Article] [PMID:
19442236 PubMed - indexed for MEDLINE]
Estimation of Affinity of HLA-A*0201 Restricted CTL
Epitope Based on the SCORE Function
L. Zhi-Hua, W. Huai-Liang, Z. Bo, W.
Yuan-Qiang, L. Yong and W. Yu-Zhang
A set of 70 peptides with affinity for the class I MHC
HLA-A*0201 molecule was subjected to quantitative analyses
of structure-affinity relationship based on the SCORE function
with good results (r2=0.6982,
q2=0.6188, RMS=0.280). Then
the ‘leave-one-out’ cross-validation (LOO-CV)
and an outer test set including 18 outer samples were used
to validate the QSAR model, and the results show that the
QSAR model has good predictability for outside samples. Statistical
analysis showed that the hydrophobic and hydrogen bond interaction
played a significant role in peptide-MHC molecule binding.
The study also provided useful information for structure modification
of CTL epitope, and laid theoretical base for molecular design
of therapeutic vaccine.
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