ABSTRACT
As the number of files in the Protein Data Bank (PDB) exceeded 50,000 (representing around 10,000 protein domains at 95% level of sequence identity), it is becoming increasingly important to develop the understanding of the protein function and the next level of subcellular structural organization.1,2 This, among other aspects, requires understanding of what other biological molecules or cellular
Introduction ............................................................................................................ 185 Characterizing Molecular Interfaces ...................................................................... 187
Comprehensive Sets of Transient Molecular Interactions in 3D ....................... 187 Properties and Flexibility of Transient Molecular Interfaces ............................ 188
Predicting Protein-Protein Interactions ................................................................. 192 Physicochemical Properties or Evolutionary Patterns? ..................................... 192 Protein Interface Prediction with REVCOM .................................................... 196 Optimal Docking Area (ODA) .......................................................................... 196 Protein Interface Recognition (PIER) ............................................................... 198 Predicting Membrane Interfaces: MODA .........................................................200 Protein Docking ................................................................................................200
Protein Interactions with Small Molecules ............................................................202 Pocketome Based on Gaussian Convolution of the Lennard-Jones Potential ...203 Cross-Docking of a Ligand to a Single Receptor Conformation with the ICM Algorithm Overcomes Limited Induced Fit ..............................................203 Advanced Approaches to Induced Fit in Ligand Docking ................................204 Ligand Screening and Profiling .........................................................................204
Conclusions ............................................................................................................205 Acknowledgments ..................................................................................................205 References ..............................................................................................................205
structures interact with each domain, which residues are involved in this interaction (e.g., References 3 and 4), and what conformational changes accompany the binging. Structure-based computational approaches to these questions invariably face the issue of protein flexibility, which is further complicated by the existence of unstructured, partially structured, or conditionally structured interfaces.5 While the dream of predictive millisecond-scale molecular dynamics serving as a “computational microscope” persists (K. Schulten, award lecture at the ISQBP meeting in Ascona, 2008; also Reference 6) and may even be getting more tangible as computers become faster, the ability to make reliable predictions on the basis of such trajectory is still lacking.
