Computation of Biomolecular Structures: Achievements, Problems, and Perspectives

Computational techniques have become an indispensable part of Molecular Biology, Biochemistry, and Molecular Design. In conjunction with refined experimental methods and powerful hardware, they enable us to analyze and visualize biomolecular structures, simulate their motions and to a variable degree understand their physicochemical properties and function. In addition, they provide essentially the only way to analyze and correlate the astronomical amounts of experimental sequence and structural data accumulating in international databases. We have good reasons to believe that further advances in this area will eventually enable us to predict with sufficient accuracy many structural and functional properties of fairly large biomolecules, given their sequence and specified environmental conditions. However, it is also important to realize that in achieving this goal, we encounter several serious problems of conceptual and methodological nature, the solution of which requires new approaches and algorithms. For example, we need better force fields, more efficient optimization routines, an adequate description of electrostatics and hydration, reliable methods to compute free energies, and ways to extent the length of molecular dynamics simulations by several orders of magnitude.

Table of Contents:
Structure Analysis and Prediction.- Structure Determination from NMR — Application to Crambin.- From Sequence Similarity to Structural Homology of Proteins.- Equilibrium Distribution of Secondary Structures for Large RNA.- Doing sequence analysis by inspecting the order in which neural networks learn.- Computational Approaches to Nucleic Acid Structure.- A New Program for the Analysis of Nucleic Acid Structure: Implications for Nucleic Acid Structure Interpretation.- Modeling DNA Backbone Structures.- Specific Systems.- Serine and Cysteine Proteases and their Natural Inhibitors: Structures and Implications for Function and Drug Design.- Principles of Protein — Protein Recognition in Protease-Inhibitor and Antigen-Antibody Complexes.- Subtleties in Designing DNA Sequence Specific Ligands.- The Structure of DNA Four-Way Junctions.- Physical Chemistry and Dynamics.- Rapid Conformational Investigations of Organic Molecules.- Dynamics of DNA Oligomers: Harmonic and Anharmonic Motions.- Surface Boundary Conditions: A Simulation Model for Macromolecules.- Computation of Ionic Distributions around Charged Biomolecular Structures using the PMF Approach.- Formal Aspects of the Potential of Mean Force Approach.- List of Contributors.