Computational Screening of CCR5 Inhibitors as Potential Entry Inhibitor Microbicides Using 3D-QSAR Studies, Docking and Molecular Dynamics Simulation

Title:Computational Screening of CCR5 Inhibitors as Potential Entry Inhibitor Microbicides Using 3D-QSAR Studies, Docking and Molecular Dynamics Simulation

Volume: 15 Issue: 4

Author(s): Radhika Ramachandran, Muthusankar Aathi, Durairaj D. Ruban and Shanmughavel Piramanyagam*

Affiliation:

• Department of Bioinformatics, Bharathiar University, Coimbatore-641046,India

Keywords: CCR5 antagonists, docking, 3D-QSAR, microbicides, molecular dynamics, pharmacophore.

Abstract: Background: The chemokine receptor CCR5 acts as a co-receptor for HIV binding and it is considered as an important target by CCR5 antagonists. Entry inhibitor based microbicides gain much importance nowadays as these drugs act at an early stage of HIV lifecycle and thus hinder the viral replication process in humans. The present study intends to identify a CCR5 antagonist which could be developed as a microbicide using computational approaches.

Methods: The pharmacophore modeling and 3D QSAR studies was used to screen CCR5 antagonists with enhanced antagonist activity. The docking studies ranked the compounds according to their bind- ing affinity and molecular dynamics simulation validated the stability of the enzymeligand complex.

Results: A five point pharmacophore hypothesis HHPRR (2 hydrophobic; 1 positively ionisable; 2 aromatic ring) was generated. A statistically significant 3D QSAR model with 3 PLS factors was gen- erated for common pharmacophore hypothesis HHPRR.3 with good correlation coefficient value (R²=0.7483). The docking studies revealed that molecular interaction of CCR5 antagonists having good binding affinity are better than the microbicides taken for this study. The QSAR maps revealed the regions as a combined effect of hydrogen bond donors, hydrogen bond acceptors and hydrophobic groups which denoted the substitution of groups indicating the favorable and unfavorable regions for antagonist activity of hydroxypiperidine derivatives. The docking analysis and molecular dynamics simulation screened and validated CCR5 antagonists.

Conclusion: The present study was successful in identifying a CCR5 antagonist which could be developed as a microbicide.

Cite this article as:

Ramachandran Radhika, Aathi Muthusankar, Ruban D. Durairaj and Piramanyagam Shanmughavel*, Computational Screening of CCR5 Inhibitors as Potential Entry Inhibitor Microbicides Using 3D-QSAR Studies, Docking and Molecular Dynamics Simulation, Current HIV Research 2017; 15 (4) . https://dx.doi.org/10.2174/1570162X15666170106124216

DOI https://dx.doi.org/10.2174/1570162X15666170106124216	Print ISSN 1570-162X
Publisher Name Bentham Science Publisher	Online ISSN 1873-4251