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Recent Development of Scoring Functions on Small Molecular Docking

소분자 도킹에서의 평가함수의 개발 동향

  • Chung, Hwan Won (Computational Science Center, Future Fusion Technology Division, Korea Institute of Science and Technology) ;
  • Cho, Seung Joo (Department of Cellular and Molecular Medicine & Center for Resitance Cells, College of Medicine, Chosun University)
  • 정환원 (한국과학기술연구원 계산과학연구센터) ;
  • 조승주 (조선대학교 의과대학 세포분자 연구센터)
  • Received : 2010.01.15
  • Accepted : 2010.03.20
  • Published : 2010.03.31

Abstract

Molecular docking is a critical event which mostly forms Van der waals complex in molecular recognition. Since the majority of developed drugs are small molecules, docking them into proteins has been a prime concern in drug discovery community. Since the binding pose space is too vast to cover completely, many search algorithms such as genetic algorithm, Monte Carlo, simulated annealing, distance geometry have been developed. Proper evaluation of the quality of binding is an essential problem. Scoring functions derived from force fields handle the ligand binding prediction with the use of potential energies and sometimes in combination with solvation and entropy contributions. Knowledge-based scoring functions are based on atom pair potentials derived from structural databases. Forces and potentials are collected from known protein-ligand complexes to get a score for their binding affinities (e.g. PME). Empirical scoring functions are derived from training sets of protein-ligand complexes with determined affinity data. Because non of any single scoring function performs generally better than others, some other approaches have been tried. Although numerous scoring functions have been developed to locate the correct binding poses, it still remains a major hurdle to derive an accurate scoring function for general targets. Recently, consensus scoring functions and target specific scoring functions have been studied to overcome the current limitations.

Keywords

References

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