Refined models for computer calculations in protein engineering

Robson, Barry; Platt, Eric

doi:10.1016/0022-2836(86)90309-8

Cited by 53 publications

(14 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The variable dihedral angles are the backbone 4 and $ and the side-chain x's, as described by Robson and Platt (1986). We use a united-atom representation where only the polar hydrogens that are capable of forming hydrogen bonds are taken into account.…”

Section: Methodsmentioning

confidence: 99%

Monte Carlo study of the effect of β₂‐microglobulin on the binding cleft of the HLA‐A2 complex

et al. 1994

View full text Add to dashboard Cite

Peptide recognition by class I products of the major histocompatibility complex requires association of the class I heavy chain with /32-microglobulin. We present results of Monte Carlo simulations of the @-pleated sheet floor of the human class I MHC molecule, HLA-A2, with and without P,-microglobulin. We find a significant effect of µglobulin on the side chains of residues near a region that would accommodate the C-terminus of a bound peptide. By modeling simultaneously each loop and its neighboring strand at either end of the class I cleft, we find that P2-microglobulin restricts the conformational space of residues that are central to binding peptides. The effect is most pronounced for R97 and H114 and somewhat less important for Y99 and Y116, the latter forming strong hydrogen bonds with neighboring residues in the heavy chain itself.

show abstract

Section: Methodsmentioning

confidence: 99%

Monte Carlo study of the effect of β₂‐microglobulin on the binding cleft of the HLA‐A2 complex

et al. 1994

View full text Add to dashboard Cite

show abstract

“…Currently, we have standard rule bases in use for complementary design to protein receptors and DNA and for similar design to general organic molecules and peptides. Three sets of atom types are catered for at the present time: AMBER [43,44], POLY [45] and COS-MIC [46]. Secondly, the rule base can be edited by the user.…”

Section: Design-model Generation Modulementioning

confidence: 99%

PRO_LIGAND: An approach to de novo molecular design. 1. Application to the design of organic molecules

Clark

Frenkel

Levy

et al. 1995

J Computer-Aided Mol Des

121

View full text Add to dashboard Cite

An approach to de novo molecular design, PRO-LIGAND, has been developed that, in the environment of a large, integrated molecular design and simulation system, provides a unified framework for the generation of novel molecules which are either similar or complementary to a specified target. The approach is based on a methodology that has proved to be effective in other studies--placing molecular fragments upon target interaction sites-but incorporates many novel features such as the use of a rapid graph-theoretical algorithm for fragment placing, a generalised driver for structure generation which offers a large variety of fragment assembly strategies to the user and the pre-screening of library fragments. After a detailed description of the relevant modules of the package, PRO-LIGAND's efficacy in aiding rational drug design is demonstrated by its ability to design mimics of methotrexate and potential inhibitors for dihydrofolate reductase and HIV-1 protease.

show abstract

“…The force field of Robson and Platt [9] was used. This force field has been carefully calibrated to reproduce quantum-mechanical and experimental data for a variety of model peptide systems.…”

Section: Force Fieldmentioning

confidence: 99%

Novel algorithms for searching conformational space

Byrne

Platt

et al. 1994

J Computer-Aided Mol Des

Self Cite

View full text Add to dashboard Cite

The modelling of biological molecules by molecular dynamics is beset by a range of problems. The most important of these is the multiple-minima problem. The deep metastable minima can cause difficulties in proper equilibration of a molecular system and result in the simulated system being trapped in a long-lived metastable state. One way to overcome these problems is to re-engineer the 'Newtonian Rules' in order to more efficiently search conformational space. Re-engineering of the 'Newtonian Rules' implies a redesign of the physical laws arising from them. This is done in various ways by the RUSH, Hybrid Monte Carlo and PEACS algorithms. This paper explores applications of these algorithms, and compares them to a traditional molecular dynamics method.

show abstract

Refined models for computer calculations in protein engineering

Cited by 53 publications

References 33 publications

Monte Carlo study of the effect of β₂‐microglobulin on the binding cleft of the HLA‐A2 complex

Monte Carlo study of the effect of β₂‐microglobulin on the binding cleft of the HLA‐A2 complex

PRO_LIGAND: An approach to de novo molecular design. 1. Application to the design of organic molecules

Novel algorithms for searching conformational space

Contact Info

Product

Resources

About

Refined models for computer calculations in protein engineering

Cited by 53 publications

References 33 publications

Monte Carlo study of the effect of β2‐microglobulin on the binding cleft of the HLA‐A2 complex

Monte Carlo study of the effect of β2‐microglobulin on the binding cleft of the HLA‐A2 complex

PRO_LIGAND: An approach to de novo molecular design. 1. Application to the design of organic molecules

Novel algorithms for searching conformational space

Contact Info

Product

Resources

About

Monte Carlo study of the effect of β₂‐microglobulin on the binding cleft of the HLA‐A2 complex

Monte Carlo study of the effect of β₂‐microglobulin on the binding cleft of the HLA‐A2 complex