Search algorithms and scoring methods in protein-ligand docking

Accurate structural modeling and correct prediction of activity are the two aims of docking studies The identification of molecular features and modifications in compounds in order to improve the potency are the other difficult issues to understand Docking process is a multi step process in which each step introduces one or more additional degrees of complication The generation of ligand conformations and to locate at the most stable state in the energy landscape is the first step in the process of docking To treat ligand flexibility and to some extent protein flexibility different search algorithms are utilized The evaluation and ranking of envisaged ligand conformations are executed by scoring functions Scoring functions make various assumptions and simplifications and do not fully account for a number of physical phenomena that determine molecular recognition This chapter focuses on the methodological development of the search algorithms and scoring functions including limitations and advantages