Structure and thermodynamics of RNA-protein binding: using molecular dynamics and free energy analyses to calculate the free energies of binding and conformational change.

P A Kollman, C M Reyes

Journal: Journal of molecular biology 2000;297(5):1145-58

PMID: 10764579

Full Text on Elsevier Science View on PubMed

Abstract

An adaptive binding mechanism, requiring large conformational rearrangements, occurs commonly with many RNA-protein associations. To explore this process of reorganization, we have investigated the conformational change upon spliceosomal U1A-RNA binding with molecular dynamics (MD) simulations and free energy analyses. We computed the energetic cost of conformational change in U1A-hairpin and U1A-internal loop binding using a hybrid of molecular mechanics and continuum solvent methods. Encouragingly, in all four free energy comparisons (two slightly different proteins, two different RNAs), the free macromolecule was more stable than the bound form by the physically reasonable value of approximately 10 kcal/mol. We calculated the absolute binding free energies for both complexes to be in the same range as that found experimentally.

Address: Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94122-0446, USA.

DOI: 10.1006/jmbi.2000.3629

Link outs

Free resources

Other Literature Sources:

https://www.lens.org/lens/search/patent/list?q=ref...

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0022...

MeSH Terms: Amino Acid Sequence, Computer Simulation, Humans, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Osmolar Concentration, Protein Binding, Protein Structure, Secondary, RNA, RNA-Binding Proteins, Ribonucleoprotein, U1 Small Nuclear, Salts, Solvents, Static Electricity, Thermodynamics