ABSTRACT
Proteins, the end products of the information contained in the genome of any organism, are the active elements of life whose chemical activities regulate all cellular activities. According to Monod, it is in the protein that lies the secret of life. As a consequence, studies of protein sequences, structures, and functions occupy a central role in molecular biology. Genomics projects aim at mapping the genetic information of as many organisms as possible, which contributed to an exponential growth in our knowledge of the protein sequence space (more than 6.6 million protein sequences were available as of July 2008). In parallel, structural genomics projects (Sali 1998; Baker and Sali 2001) aim at covering the corresponding protein structure space, yielding another exponential growth in the number of protein structures derived from experimental data; currently, there are more than 48,000 protein structures in the Protein Data Bank (PDB; Berman et al. 2000). Finally, a major effort is put
Physics-Based Force Fields ................................................................................... 258 Stability of Protein Sequences: Application to Sequence Design ................ 259 The Denatured State .....................................................................................260 Computing the Free Energy with Explicit Water Representation ................. 261
Internal Energy ................................................................................. 261 Entropy ............................................................................................264
