Computational Drug Discovery and Design

Chapter 12

Evaluation of Protein–Ligand Docking by Cyscore

Yang Cao, Wentao Dai, and Zhichao Miao

Abstract

Protein–ligand docking is a powerful method in drug discovery. The reliability of docking can be quantified
by RMSD between a docking structure and an experimentally determined one. However, most experimen-
tally determined structures are not available in practice. Evaluation by scoring functions is an alternative for
assessing protein–ligand docking results. This chapter first provides a brief introduction to scoring methods
used in docking. Then details are provided on how to use Cyscore programs. Finally it describes a case study
for evaluation of protein–ligand docking.

Key wordsBinding pocket, Cyscore, CurvatureSurface, Protein–ligand docking, Scoring function

1 Introduction

Protein–ligand docking is prediction of the complex structure

formed by a ligand and a target protein with known 3D structures

respectively. It has been widely applied to drug discovery and

biological studies [1–3]. Modern docking methods, established

on the historical “lock-and-key” and “induced-fit” theories, are

generally constituted of a search algorithm and a scoring function.

The search algorithm explores possible binding positions and

orientations, and may account for the flexibility of ligand or protein

during the searching, while the scoring function evaluates the

binding free energy of conformations generated by the search

algorithm. Because the searching and scoring processes are

repeated thousands of times in order to find the most energy-

favorable binding conformation, docking is computationally

expensive. In the last few decades, tens of algorithms have been

proposed to overcome docking problem [2, 4–9]. Nowerdays the

state-of-the-art docking programs could achieve high accuracy

[2, 10, 11], however, failures still appear in practice. One of the

main reasons is due to the trade-off between computational speed

and prediction accuracy: reducing the number of freedom and

Mohini Gore and Umesh B. Jagtap (eds.),Computational Drug Discovery and Design, Methods in Molecular Biology, vol. 1762,
https://doi.org/10.1007/978-1-4939-7756-7_12,©Springer Science+Business Media, LLC, part of Springer Nature 2018

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