NDLI: Conformational analysis of a farnesyltransferase peptide inhibitor, CVIM

Content Provider	Springer Nature Link
Author	Carlacci, Louis
Copyright Year	2000
Abstract	The conformational states of the peptide Cys-Val-Ile-Met (or CVIM) were computed and characterized. CVIM inhibits farnesylation of the Ras oncogene product, p21$^{ras}$, at the cysteine residue of the C-terminal segment. CVIM is active in an extended conformation. A similar peptide (KTKCVFM) appears to bind the enzyme in the Type I bend conformation. In the present study, the conformations of CVIM were computed in an aqueous environment with the peptide in the zwitterionic state. Solvation free energy based on solvent accessible surface area and a distance dependent dielectric were used in the calculations. Final conformations of multiple independent Monte Carlo simulated annealing (MCSA) conformational searches were used as starting points for Metropolis Monte Carlo (MMC) runs. Conformations saved at intervals during MMC runs were analyzed. Conformers were separated by interactive clustering in dihedral angle coordinates. The four lowest energy conformers corresponding to a Type I bend, extended, AB-bend, and BA-bend were within 0.3 kcal/mol of each other, and dominant in terms of population. The Type I bend and extended conformers were supported by the binding studies. The extended conformer was the most populated. In the AB-bend conformer, `A' indicates the α-helix conformation of Val, and `B' indicates the β-strand conformation of Ile. The AB- and BA-bend conformations differed from the extended conformation in the value of Val ψ and Ile ψ, respectively, and from the Type I bend conformation in the value of Ile ψ and Val ψ, respectively. The four lowest energy conformers were characterized in terms of energy, density of low energy conformations (or entropy), structure, side chain rotamer fraction population, and interatomic distances.
Starting Page	369
Ending Page	382
Page Count	14
File Format	PDF
ISSN	0920654X
Journal	Journal of Computer-Aided Molecular Design
Volume Number	14
Issue Number	4
e-ISSN	15734951
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2000-01-01
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Computer Applications in Chemistry Physical Chemistry Animal Anatomy / Morphology / Histology
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

Conformational analysis of [Met5]-enkephalin: Solvation and ionization considerations

Camdas: An automated conformational analysis system using molecular dynamics

Conformational analysis of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, based on quantum mechanical calculations

A proposed bioactive conformation of Peptide T

Conformational energy penalties of protein-bound ligands

Protein farnesyltransferase: Flexible docking studies on inhibitors using computational modeling

Fragment-based drug discovery

Thermodynamic conformational analysis and structural stability of the nicotinic analgesic ABT-594

Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics

Conformational analysis of a farnesyltransferase peptide inhibitor, CVIM

Similar Documents

Conformational analysis of [Met5]-enkephalin: Solvation and ionization considerations

Camdas: An automated conformational analysis system using molecular dynamics

Conformational analysis of nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, based on quantum mechanical calculations

A proposed bioactive conformation of Peptide T

Conformational energy penalties of protein-bound ligands

Protein farnesyltransferase: Flexible docking studies on inhibitors using computational modeling

Fragment-based drug discovery

Thermodynamic conformational analysis and structural stability of the nicotinic analgesic ABT-594

Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics

Conformational analysis of a farnesyltransferase peptide inhibitor, CVIM