title: The Augmenting Effects of Desolvation and Conformational Energy Terms on the Predictions of Docking Programs against mPGES-1.
abstract: In this study we introduce a rescoring method to improve the accuracy of docking programs against mPGES-1. The rescoring method developed is a result of extensive computational study in which different scoring functions and molecular descriptors were combined to develop consensus and rescoring methods. 127 mPGES-1 inhibitors were collected from literature and were segregated into training and external test sets. Docking of the 27 training set compounds was carried out using default settings in AutoDock Vina, AutoDock, DOCK6 and GOLD programs. The programs showed low to moderate correlation with the experimental activities. In order to introduce the contributions of desolvation penalty and conformation energy of the inhibitors various molecular descriptors were calculated. Later, rescoring method was developed as empirical sum of normalised values of docking scores, LogP and Nrotb. The results clearly indicated that LogP and Nrotb recuperate the predictions of these docking programs. Further the efficiency of the rescoring method was validated using 100 test set compounds. The accurate prediction of binding affinities for analogues of the same compounds is a major challenge for many of the existing docking programs; in the present study the high correlation obtained for experimental and predicted pIC50 values for the test set compounds validates the efficiency of the scoring method.
authors: Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, Dharamshala, Himachal Pradesh- 176215, India.
authors: Ashish
authors: A
authors: Gupta
authors: Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, Dharamshala, Himachal Pradesh- 176215, India.
authors: Neha
authors: N
authors: Chaudhary
authors: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana- 500046, India.
authors: Kumar Reddy
authors: KR
authors: Kakularam
authors: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana- 500046, India.
authors: Reddanna
authors: R
authors: Pallu
authors: Centre for Computational Biology and Bioinformatics, School of Life Sciences, Central University of Himachal Pradesh, Dharamshala, Himachal Pradesh- 176215, India.
authors: Aparoy
authors: A
authors: Polamarasetty
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D062105:Molecular Docking Simulation; D000071876:Prostaglandin-E Synthases; D011487:Protein Conformation; D018709:Statistics, Nonparametric; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases