Medicinal Chemistry Research

, Volume 21, Issue 12, pp 4060–4068

In silico screening of indinavir-based compounds targeting proteolytic activity in HIV PR: binding pocket fit approach

  • Chandrabose Selvaraj
  • Sanjeev Kumar Singh
  • Sunil Kumar Tripathi
  • Karnati Konda Reddy
  • Murugappan Rama
Original Research

DOI: 10.1007/s00044-011-9941-5

Cite this article as:
Selvaraj, C., Singh, S.K., Tripathi, S.K. et al. Med Chem Res (2012) 21: 4060. doi:10.1007/s00044-011-9941-5

Abstract

The intense research on small molecule inhibitors of Human immunodeficiency virus (HIV)-protease (PR) has produced a diverse class of chemical scaffolds which includes clinically available HIV PR inhibitors (PRI). Till now, these inhibitors are insignificant for targeting proteolytic activity and few drug molecules on alterations can enhance the inhibition of PR enzyme. Here, we developed a method for screening of new hits from Cambridge structural database, based on binding mode of indinavir interaction participating atoms. Knowledge-based ligand screening technique approximately informs that new hits are also having same binding mode-like indinavir interaction patterns. Considering the importance of ligand fitting in binding pocket, we developed induced-fit models for each compound and we obtained accurate energy values in terms of binding and interaction energy. We found that newly search molecules are interacting better than known drug—indinavir and these new compounds are comparatively having better drug-like property. Finally, we demonstrated that pocket specific docking, energy utilization, interactions, and ADME for screened compounds are showing new hit compounds of indinavir are better HIV PRI and these new compounds can also show better activity in in vivo and in vitro conditions.

Keywords

Binding energy HIV CSD Indinavir Interaction energy Induced-fit docking Protease 

Abbreviations

CSD

Cambridge structural database

OPLS

Optimized potential for liquid simulation

IFD

Induced-fit docking

PR

Protease

PRI

Protease inhibitor

Supplementary material

44_2011_9941_MOESM1_ESM.doc (1 mb)
Supplementary material 1 (DOC 1063 kb)

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Chandrabose Selvaraj
    • 1
  • Sanjeev Kumar Singh
    • 1
  • Sunil Kumar Tripathi
    • 1
  • Karnati Konda Reddy
    • 1
  • Murugappan Rama
    • 1
  1. 1.Computer Aided Drug Design and Molecular Modeling Laboratory, Department of BioinformaticsAlagappa UniversityKaraikudiIndia