ABSTRACT
There are two molecular processes that are essential for living bodies to maintain their life: the molecular recognition, and the self-organization or self-assembly. Binding of a substrate by an enzyme is an example of the molecular recognition, while the protein folding is a good example of the self-organization process. The two processes are further governed by the other two physicochemical processes: solvation and the structural fluctuation. In the present article, the studies concerning the two molecular processes carried out by Hirata and his coworkers, based on the statistical mechanics of molecular liquids or the RISM/3D-RISM theory, are reviewed.
Subject(s)
Chemical Phenomena , Molecular Docking Simulation , Molecular Dynamics Simulation , Algorithms , Drug Discovery/methods , Models, Theoretical , Solvents/chemistry , Structure-Activity Relationship , Thermodynamics , Water/chemistryABSTRACT
Researchers studying biomolecules require easy-to-use, customizable tools allowing them to effectively use other molecular science packages written for molecular dynamics (MD), quantum chemistry, statistical mechanics, and molecular graphics. This paper presents a Scala tool for the computational science of biomolecules (STCSB) developed in Scala, which allows users to prepare and run MD simulations, as well as perform three-dimensional reference interaction site model (3D-RISM) calculations of biomolecules. Features of the STCSB include the following: (1) a cross-platform application running on a Java virtual machine; (2) handling hierarchical XML-based data formats such as the protein data bank markup language (PDBML); (3) prepared application programming interfaces (APIs) with both character user interface (CUI) and graphical user interface (GUI) options; (4) prepared APIs for molecular graphics; and (5) a scalable source code based on the Model-View-Controller (MVC) architectural pattern.
ABSTRACT
The role of Mg2+ ions during precursor formation in DNA hydrolysis by the homodimeric restriction enzyme EcoRV was elucidated based on the 3D-reference interaction site model (RISM) theory and the molecular dynamics (MD) simulation. From an analysis of the spatial distribution of Mg2+ in an active site using 3D-RISM, we identified a new position for Mg2+ in the X-ray EcoRV-DNA complex structure ( 1rvb ). We refer to the position as site IV. Site IV is almost at the same position as that of a Ca2+ ion in the superimposed X-ray crystallographic active-site structure of the PvuII-DNA complex ( 1f0o ). 3D-RISM was also used to locate the position of water molecules, including the water nucleophile at the active site. MD simulations were carried out with the initial structure having two Mg2+ ions at site IV and at site I*, experimentally identified by Horton et al., to find a stable complex structure in which the DNA fragment was rearranged to orient the scissile bond direction toward the water nucleophile. The equilibrium active-site structure of the EcoRV-DNA complex obtained from the MD simulation was similar to the superimposed X-ray crystallographic structure of the BamHI-DNA complex ( 2bam ). In the active-site structure, two metal ions have almost the same position (≤1.0 Å) as that of 2bam , and the scissile phosphate is twisted to orient the scissile bond toward the water nucleophile, as is the case in 2bam . We propose the equilibrium active-site structure obtained in this study as a precursor for the hydrolysis reaction of EcoRV.
Subject(s)
DNA/metabolism , Escherichia coli Proteins/metabolism , Magnesium/metabolism , Site-Specific DNA-Methyltransferase (Adenine-Specific)/metabolism , Water/metabolism , Catalysis , Catalytic Domain , DNA/chemistry , Escherichia coli/enzymology , Escherichia coli Proteins/chemistry , Hydrolysis , Magnesium/chemistry , Molecular Dynamics Simulation , Protein Binding , Site-Specific DNA-Methyltransferase (Adenine-Specific)/chemistry , Water/chemistryABSTRACT
We have made a stereoscopic viewing system for a large assembly of proteins using OpenRasmol. The stable version 2.7.1 of OpenRasmol is modified for the system, which uses an eye-ware instead of trained bare-eyes. Software rendering and other benefits in OpenRasmol are reserved. A 3-D graphic board is used just for the active stereo method, not for the acceleration of rendering. Our modification is simple one. In the results, an actin filament of 16-mers, where one actin monomer has about 400 residues, in space filling model can be rendered in stereoscopic viewing mode and can be made one turn within 10 seconds as quick as non-stereoscopic mode. Other 3-D molecular graphics programs with 3-D accelerator boards cannot render such a large assembly of molecules in stereoscopic usage mode as quickly as the modified OpenRasmol. An attractive application of our system is stereoscopic viewing with a large 200 inch screen in passive stereo method. Simultaneous usage is available for more than 100 persons with inexpensive eye-wares. The large screen allows us to investigate an interior of a groove in an actin filament in detail. Our modified OpenRasmol is distributed following the license, RASLIC, as an open source code at our web site (www.irisa-lab.bio.kyutech.ac.jp/openrasmol), where video files showing rendering speeds of our modified OpenRasmol are also available.
