Integration of genetic virtual screening patterns and latent multivariate modeling techniques for QSAR optimization based on combinations and/or interactions between peptides and proteins  

作　　者：LI ZhiLiang TIAN FeiFei WU ShiRong YANG ShanBin YANG ShengXi ZHOU Yuan ZHANG QiaoXia QIN RenHui MEI Hu CHEN Gang LI GenRong 

机构地区：[1]Key Laboratory for Systematic Chemobiomedical Science and Technology under Chongqing Municipality,College of Chemistry and Chemical Engineering,Chongqing University,Chongqing 400044,China [2]State Key Laboratory for Chemobiosensors and Chemobiometrics under MOST,Hunan University,Changsha 410012,China [3]Key Laboratory for Biomechanics and Biomedical Engineering under both Ministry of Education and Chongqing Municipality,Col-lege of Life Science and Bioengineering,Chongqing University,Chongqing 400044,China [4]Technology Centre for Life Sciences and Biotechnology,Singapore Polytechnic,500 Dover Road,Singapore 139651,Singapore

出　　处：《Science China Chemistry》2008年第5期487-496,共10页中国科学（化学英文版）

基　　金：the National Chunhui Project Foundation (Grant No. 99-4-4+37);the Fok-Yingtung Educational Foundation (Grant No. 98-7-6);the State New Drug Project (Grant No. 1996ND1035A01);the Chongqing Municipality Applied Funda-mental Science Fund (Grant No. 01-3-6);Juche Academic Innovation Foundation for Science and Technology (Grant No. 03ZY12XT06);Chongqing University Subject Constructive Fund (Grant No. 04-10-10);State Key Laboratory for Chemobiosensors and Chemometrics under MOST Fund (Grant No. 2005012);National High Technology Research and Development (863) Program of China (Grant No. 2006AA02Z312)

摘　　要：Both the concept and the model of snug quantitative structure-activity relationship (QSAR) were proposed and developed for molecular design through constructing QSAR based on some known mode of receptor/ligand interactions. Many disadvantages of traditional models can be avoided by using the proposed method because the traditional models only determined upon molecular structural features in sample sets themselves. A genetic virtual screening of peptide/protein combinations (GVSPPC) is proposed for the first time by utilizing this idea to examine peptide/protein affinity activities. A genetic algorithm (GA) was developed for screening combinative targets with an interaction mode for virtual receptors. GVSPPC succeeds in disposing difficulties in rational QSAR, in order to search for the ligand/receptor interactions on conditions of unknown structures. Some bioactive oligo-/poly-peptide systems covering 58 angiotensin converting enzyme (ACE) inhibitors and 18 double site mutation residues in camel antibody protein cAb-Lys3 were investigated by GVSPPC with satisfactory results (R cu 2 > 0.91, Q cv 2 > 0.86, E RMS = 0.19?0.95), respectively, which demonstrates that GVSPPC is more interpretable in the ligand-receptor interaction than the traditional QSAR method.Both the concept and the model of snug quantitative structure-activity relationship (QSAR) were pro-posed and developed for molecular design through constructing QSAR based on some known mode of receptor/ligand interactions. Many disadvantages of traditional models can be avoided by using the proposed method because the traditional models only determined upon molecular structural features in sample sets themselves. A genetic virtual screening of peptide/protein combinations (GVSPPC) is proposed for the first time by utilizing this idea to examine peptide/protein affinity activities. A genetic algorithm (GA) was developed for screening combinative targets with an interaction mode for virtual receptors. GVSPPC succeeds in disposing difficulties in rational QSAR,in order to search for the ligand/receptor interactions on conditions of unknown structures. Some bioactive oligo-/poly-peptide systems covering 58 angiotensin converting enzyme (ACE) inhibitors and 18 double site mutation residues in camel antibody protein cAb-Lys3 were investigated by GVSPPC with satisfactory results (R 2 cu>0.91,Q 2 cv > 0.86,ERMS=0.19-0.95),respectively,which demonstrates that GVSPPC is more inter-pretable in the ligand-receptor interaction than the traditional QSAR method.

关 键 词：GENETIC virtual screening of peptide-protein combination (GVSPPC) quantitative STRUCTURE-ACTIVITY relationship (QSAR) GENETIC algorithm (GA) partial least square (PLS) principal component analysis (PCA) 

分 类 号：Q78[生物学—分子生物学]