Abstract
Bioactive peptides and peptidomimetics play a pivotal role in the regulation of many biological processes such as cellular apoptosis, host defense, and biomineralization. In this work, we develop a novel structural matrix, Index of Natural and Non-natural Amino Acids (NNAAIndex), to systematically characterize a total of 155 physiochemical properties of 22 natural and 593 non-natural amino acids, followed by clustering the structural matrix into 6 representative property patterns including geometric characteristics, H-bond, connectivity, accessible surface area, integy moments index, and volume and shape. As a proof-of-principle, the NNAAIndex, combined with partial least squares regression or linear discriminant analysis, is used to develop different QSAR models for the design of new peptidomimetics using three different peptide datasets, i.e., 48 bitter-tasting dipeptides, 58 angiotensin-converting enzyme inhibitors, and 20 inorganic-binding peptides. A comparative analysis with other QSAR techniques demonstrates that the NNAAIndex method offers a stable and predictive modeling technique for in silico large-scale design of natural and non-natural peptides with desirable bioactivities for a wide range of applications.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Aluminum Silicates / metabolism
-
Amino Acids / chemistry
-
Amino Acids / metabolism*
-
Angiotensin-Converting Enzyme Inhibitors / chemistry
-
Angiotensin-Converting Enzyme Inhibitors / pharmacology
-
Least-Squares Analysis
-
Peptidomimetics / chemical synthesis*
-
Peptidomimetics / chemistry
-
Peptidomimetics / pharmacology
-
Protein Binding / drug effects
-
Quantitative Structure-Activity Relationship
-
Reproducibility of Results
Substances
-
Aluminum Silicates
-
Amino Acids
-
Angiotensin-Converting Enzyme Inhibitors
-
Peptidomimetics
-
mica
Grants and funding
This work was supported by grants from the Natural Science Foundation Project of Chongqing CSTC (number cstc2012gg-gjhz10003), National Natural Science Foundation of China (number 10901169), Fundamental Research Funds for Central Universities (number CDJZR11 23 00 09 and number CQDXWL-2012-129), and the National Science Foundation (CAREER Award CBET-0952624 and CBET-1158447) of USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.