Performance of protein-ligand docking with CDK4/6 inhibitors: a case study

Linlu Song; Shangbo Ning; Jinxuan Hou; Yunjie Zhao; Linlu Song; Shangbo Ning; Jinxuan Hou; Yunjie Zhao

doi:10.3934/mbe.2021025

Mathematical Biosciences and Engineering

2021, Volume 18, Issue 1: 456-470. doi: 10.3934/mbe.2021025

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Performance of protein-ligand docking with CDK4/6 inhibitors: a case study

1.
Institute of Biophysics and Department of Physics, Central China Normal University, Wuhan 430079, China
2.
Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

Received: 03 September 2020 Accepted: 02 December 2020 Published: 08 December 2020

It is widely believed that tertiary protein-ligand interactions are essential in determining protein function. Currently, the structure sampling and scoring function in traditional docking methods still have limitations. Therefore, new methods for protein-ligand docking are desirable. The accurate docking can speed up the early-stage development of new drugs. Here we present a multi-source information-based protein-ligand docking approach (pmDock). In the CDK4/6 inhibitor case study, pmDock produces a substantial accuracy increases between the predicted geometry centers of ligands and experiments compared to AutoDock and SwissDock alone. Also, pmDock improves predictions for critical binding sites and captures more tertiary binding interactions. Our results demonstrate that pmDock is a reliable docking method for accurate protein-ligand prediction.
- protein-ligand docking,
- multi-source information,
- CDK4/6 inhibitor,
- structure sampling,
- scoring function,
- breast cancer
Citation: Linlu Song, Shangbo Ning, Jinxuan Hou, Yunjie Zhao. Performance of protein-ligand docking with CDK4/6 inhibitors: a case study[J]. Mathematical Biosciences and Engineering, 2021, 18(1): 456-470. doi: 10.3934/mbe.2021025

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Abstract

It is widely believed that tertiary protein-ligand interactions are essential in determining protein function. Currently, the structure sampling and scoring function in traditional docking methods still have limitations. Therefore, new methods for protein-ligand docking are desirable. The accurate docking can speed up the early-stage development of new drugs. Here we present a multi-source information-based protein-ligand docking approach (pmDock). In the CDK4/6 inhibitor case study, pmDock produces a substantial accuracy increases between the predicted geometry centers of ligands and experiments compared to AutoDock and SwissDock alone. Also, pmDock improves predictions for critical binding sites and captures more tertiary binding interactions. Our results demonstrate that pmDock is a reliable docking method for accurate protein-ligand prediction.

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