Sanjeevini: a freely accessible web-server for target directed lead molecule discovery

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Computational methods utilizing the structural and functional information help to understand specific molecular recognition events between the target biomolecule and candidate hits and make it possible to design improved lead molecules for the target.

Results

Sanjeevini represents a massive on-going scientific endeavor to provide to the user, a freely accessible state of the art software suite for protein and DNA targeted lead molecule discovery. It builds in several features, including automated detection of active sites, scanning against a million compound library for identifying hit molecules, all atom based docking and scoring and various other utilities to design molecules with desired affinity and specificity against biomolecular targets. Each of the modules is thoroughly validated on a large dataset of protein/DNA drug targets.

Conclusions

The article presents Sanjeevini, a freely accessible user friendly web-server, to aid in drug discovery. It is implemented on a tera flop cluster and made accessible via a web-interface at http://www.scfbio-iitd.res.in/sanjeevini/sanjeevini.jsp. A brief description of various modules, their scientific basis, validation, and how to use the server to develop in silico suggestions of lead molecules is provided.

Related collections

Most cited references 107

Record: found
Abstract: found
Article: not found

Improved protein-ligand docking using GOLD.

Marcel Verdonk, Jason Cole, Michael J Hartshorn … (2003)

The Chemscore function was implemented as a scoring function for the protein-ligand docking program GOLD, and its performance compared to the original Goldscore function and two consensus docking protocols, "Goldscore-CS" and "Chemscore-GS," in terms of docking accuracy, prediction of binding affinities, and speed. In the "Goldscore-CS" protocol, dockings produced with the Goldscore function are scored and ranked with the Chemscore function; in the "Chemscore-GS" protocol, dockings produced with the Chemscore function are scored and ranked with the Goldscore function. Comparisons were made for a "clean" set of 224 protein-ligand complexes, and for two subsets of this set, one for which the ligands are "drug-like," the other for which they are "fragment-like." For "drug-like" and "fragment-like" ligands, the docking accuracies obtained with Chemscore and Goldscore functions are similar. For larger ligands, Goldscore gives superior results. Docking with the Chemscore function is up to three times faster than docking with the Goldscore function. Both combined docking protocols give significant improvements in docking accuracy over the use of the Goldscore or Chemscore function alone. "Goldscore-CS" gives success rates of up to 81% (top-ranked GOLD solution within 2.0 A of the experimental binding mode) for the "clean list," but at the cost of long search times. For most virtual screening applications, "Chemscore-GS" seems optimal; search settings that give docking speeds of around 0.25-1.3 min/compound have success rates of about 78% for "drug-like" compounds and 85% for "fragment-like" compounds. In terms of producing binding energy estimates, the Goldscore function appears to perform better than the Chemscore function and the two consensus protocols, particularly for faster search settings. Even at docking speeds of around 1-2 min/compound, the Goldscore function predicts binding energies with a standard deviation of approximately 10.5 kJ/mol. Copyright 2003 Wiley-Liss, Inc.

0 comments Cited 605 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A fast flexible docking method using an incremental construction algorithm.

M Rarey, B. Kramer, T Lengauer … (1996)

We present an automatic method for docking organic ligands into protein binding sites. The method can be used in the design process of specific protein ligands. It combines an appropriate model of the physico-chemical properties of the docked molecules with efficient methods for sampling the conformational space of the ligand. If the ligand is flexible, it can adopt a large variety of different conformations. Each such minimum in conformational space presents a potential candidate for the conformation of the ligand in the complexed state. Our docking method samples the conformation space of the ligand on the basis of a discrete model and uses a tree-search technique for placing the ligand incrementally into the active site. For placing the first fragment of the ligand into the protein, we use hashing techniques adapted from computer vision. The incremental construction algorithm is based on a greedy strategy combined with efficient methods for overlap detection and for the search of new interactions. We present results on 19 complexes of which the binding geometry has been crystallographically determined. All considered ligands are docked in at most three minutes on a current workstation. The experimentally observed binding mode of the ligand is reproduced with 0.5 to 1.2 A rms deviation. It is almost always found among the highest-ranking conformations computed.

0 comments Cited 399 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules

David A. Pearlman, David A. Case, James W. Caldwell … (1995)

0 comments Cited 360 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

B Jayaram

Tanya Singh

Goutam Mukherjee

Abhinav Mathur

Shashank Shekhar

Vandana Shekhar

Conference

Journal ID (nlm-ta): BMC Bioinformatics

Journal ID (iso-abbrev): BMC Bioinformatics

Title: BMC Bioinformatics

Publisher: BioMed Central

ISSN (Electronic): 1471-2105

Publication date Collection: 2012

Publication date (Electronic): 7 December 2012

Volume: 13

Issue: Suppl 17

Page: S7

Affiliations

[1 ]Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India

[2 ]Supercomputing Facility for Bioinformatics & Computational Biology, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India

[3 ]Kusuma School of Biological Sciences, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India

Article

Publisher ID: 1471-2105-13-S17-S7

DOI: 10.1186/1471-2105-13-S17-S7

PMC ID: 3521208

PubMed ID: 23282245

SO-VID: cf6fc2aa-f194-4813-9139-2c597691a5ef

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Conference name: Asia Pacific Bioinformatics Network (APBioNet) Eleventh International Conference on Bioinformatics (InCoB2012)

Sanjeevini: a freely accessible web-server for target directed lead molecule discovery

Read this article at

Abstract

Background

Results

Conclusions

Related collections

DrugRxiv

Most cited references 107

Improved protein-ligand docking using GOLD.

A fast flexible docking method using an incremental construction algorithm.

AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules

Author and article information

Contributors

Conference

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 83

Cited by 43

Most referenced authors 2,805