NDLI: Scoring confidence index: statistical evaluation of ligand binding mode predictions

Content Provider	Springer Nature Link
Author	Zavodszky, Maria I. Stumpff Kane, Andrew W. Lee, David J. Feig, Michael
Copyright Year	2009
Abstract	Protein-ligand docking programs can generate a large number of possible binding orientations for each ligand candidate. The challenge is to identify the orientations closest to the native binding mode using a scoring method. Many different scoring functions have been developed for protein-ligand scoring, but their performance on binding mode prediction is often target-dependent. In this study, a statistical approach was employed to provide a confidence measure of scoring performance in finding close to the correct docked ligand orientations. It exploits the fact that the scores provided by an adequately performing scoring function generally improve as the ligand binding modes get closer to the correct native orientation. For such cases, the correlation coefficient of scores versus distances is expected to be highest when the most native-like orientation is used as a reference. This correlation coefficient, called the correlation-based score (CBScore), was used as an indicator of how far the docked pose was from the native orientation. The correlation between the original scores and CBScores as well as the range of CBScores were found to be good measures of scoring performance. They were combined into a single quantity, called the scoring confidence index. High values of the scoring confidence index were indicative of pronounced and relatively smooth binding energy landscapes with easily discernable global minima, resulting in reliable binding mode predictions. Low values of this index reflected rugged energy landscapes making the prediction of the correct binding mode very difficult and often unreliable. The diagnostic ability of the scoring confidence index was tested on a non-redundant set of 50 protein-ligand complexes scored with three commonly employed scoring functions: AffiScore, DrugScore and X-Score. Binding mode predictions were found to be three times more reliable for complexes with scoring confidence indices in the upper half than for cases with values in the lower half of the resulting range of 0–1.6. This new confidence measure of scoring performance is expected to be a valuable tool for virtual screening applications.
Starting Page	289
Ending Page	299
Page Count	11
File Format	PDF
ISSN	0920654X
Journal	Journal of Computer-Aided Molecular Design
Volume Number	23
Issue Number	5
e-ISSN	15734951
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-01-20
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Binding orientation Correlation-based score Energy landscape Protein-ligand docking Scoring function Computer Applications in Chemistry Animal Anatomy / Morphology / Histology Physical Chemistry
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Physical and Theoretical Chemistry Computer Science Applications

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Improving molecular docking through eHiTS’ tunable scoring function

Ligand- and receptor-based docking with LiBELa

Scoring Confidence Index: Statistical Evaluation of Ligand Binding Mode Predictions

Calculations of protein-ligand binding entropy of relative and overall molecular motions

An improved scoring function for suboptimal polar ligand complexes

D3R grand challenge 2015: Evaluation of protein–ligand pose and affinity predictions

Substantial improvements in large-scale redocking and screening using the novel HYDE scoring function

A novel scoring function for molecular docking

Robust optimization of scoring functions for a target class

Scoring confidence index: statistical evaluation of ligand binding mode predictions

Similar Documents

Improving molecular docking through eHiTS’ tunable scoring function

Ligand- and receptor-based docking with LiBELa

Scoring Confidence Index: Statistical Evaluation of Ligand Binding Mode Predictions

Calculations of protein-ligand binding entropy of relative and overall molecular motions

An improved scoring function for suboptimal polar ligand complexes

D3R grand challenge 2015: Evaluation of protein–ligand pose and affinity predictions

Substantial improvements in large-scale redocking and screening using the novel HYDE scoring function

A novel scoring function for molecular docking

Robust optimization of scoring functions for a target class

Scoring confidence index: statistical evaluation of ligand binding mode predictions