Probing some recent natural compounds from Phellinus baumii, Colletotrichum sp. and Ligustrum lucidum as heat shock protein 90 inhibitors

Abstract

Heat shock protein 90 (HSP90) is one of the most attractive targets for research on cancer treatment, and nowadays, many studies carried out for the development of effective HSP90 inhibitors. In the current study, recently published ten natural compounds have been investigated using computer aided drug design (CADD) approach. The study consists of three parts; (1) density functional theory (DFT) calculations including geometry optimizations, vibrational analyses, and molecular electrostatic potential (MEP) map calculations, (2) molecular docking and molecular dynamics (MD) simulations, and (3) binding energy calculations. In DFT calculations, Becke three-parameter hybrid functional with Lee-Yang-Parr correlation functional (B3LYP) and 6-31 + G(d,p) basis set were used. After performing molecular docking calculations, top-scoring ligand-receptor complexes were subjected to MD simulations for 100 ns to investigate the stability of the ligand-receptor complexes and the interactions in more detail. Finally, in binding energy calculations molecular mechanics with Poisson-Boltzmann surface area (MM-PBSA) method was used. The results showed that five of the investigated ten natural compounds have higher binding affinity to HSP90α than that of reference drug Geldanamycin, and could be promising compounds for future studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• HSP90
• molecular docking
• molecular dynamics simulation
• MM-P BSA
• anticancer

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The computational studies reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources) and partially at Kocaeli University. The workstation used in the calculations performed at Kocaeli University was provided within the scope of the project supported by The Scientific and Technological Research Council of Türkiye (TÜBİTAK, Project No: 122Z878).