PMID- 11566759
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20181113
IS  - 0006-3495 (Print)
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Linking)
VI  - 81
IP  - 4
DP  - 2001 Oct
TI  - Calculations of free-energy contributions to protein-RNA complex stabilization.
PG  - 1841-53
AB  - The problem of calculating binding affinities of protein-RNA complexes is 
      addressed by analyzing a computational strategy of modeling electrostatic free 
      energies based on a nonlinear Poisson-Boltzmann (NLPB) model and linear response 
      approximation (LRA). The underlying idea is to treat binding as a two-step 
      process. Solutions to the NLPB equation calculate free energies arising from 
      electronic polarizability and the LRA is constructed from molecular dynamics 
      simulations to model reorganization free energies due to conformational 
      transitions. By implementing a consistency condition of requiring the NLPB model 
      to reproduce the solute-solvent free-energy transitions determined by the LRA, a 
      "macromolecule dielectric constant" (epsilon(m)) for treating reorganization is 
      obtained. The applicability of this hybrid approach was evaluated by calculating 
      the absolute free energy of binding and free-energy changes for amino acid 
      substitutions in the complex between the U1A spliceosomal protein and its cognate 
      RNA hairpin. Depending on the residue substitution, epsilon(m) varied from 3 to 
      18, and reflected dipolar reorientation not included in the polarization modeled 
      by epsilon(m) = 2. Although the changes in binding affinities from substitutions 
      modeled strictly at the implicit level by the NLPB equation with epsilon(m) = 4 
      reproduced the experimental values with good overall agreement, substitutions 
      problematic to this simple treatment showed significant improvement when solved 
      by the NLPB-LRA approach.
FAU - Olson, M A
AU  - Olson MA
AD  - Molecular Modeling Laboratory, Department of Cell Biology and Biochemistry, 
      United States Army Medical Research Institute of Infectious Diseases, Frederick, 
      Maryland 21702, USA. molson@ncifcrf.gov
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
RN  - 0 (Macromolecular Substances)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Ribonucleoprotein, U1 Small Nuclear)
RN  - 0 (U1A protein)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Computational Biology
MH  - *Computer Simulation
MH  - Crystallography, X-Ray
MH  - Drug Stability
MH  - Macromolecular Substances
MH  - *Models, Molecular
MH  - Molecular Conformation
MH  - RNA/*chemistry
MH  - RNA-Binding Proteins/chemistry
MH  - Ribonucleoprotein, U1 Small Nuclear/*chemistry
MH  - *Thermodynamics
PMC - PMC1301660
EDAT- 2001/09/22 10:00
MHDA- 2002/01/05 10:01
PMCR- 2002/10/01
CRDT- 2001/09/22 10:00
PHST- 2001/09/22 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/22 10:00 [entrez]
PHST- 2002/10/01 00:00 [pmc-release]
AID - S0006-3495(01)75836-5 [pii]
AID - 10.1016/S0006-3495(01)75836-5 [doi]
PST - ppublish
SO  - Biophys J. 2001 Oct;81(4):1841-53. doi: 10.1016/S0006-3495(01)75836-5.