An effective all-atom potential for proteins

We describe and test an implicit solvent all-atom potential for simulations of protein folding and aggregation. The potential is developed through studies of structural and thermodynamic properties of 17 peptides with diverse secondary structure. Results obtained using the final form of the potential are presented for all these peptides. The same model, with unchanged parameters, is furthermore applied to a heterodimeric coiled-coil system, a mixed alpha/beta protein and a three-helix-bundle protein, with very good results. The computational efficiency of the potential makes it possible to investigate the free-energy landscape of these 49--67-residue systems with high statistical accuracy, using only modest computational resources by today's standards

Corrigendum:Local and macroscopic electrostatic interactions in single α-helices

The non-covalent forces that stabilise protein structures are not fully understood. One way to address this is to study equilibria between unfolded states and α-helices in peptides. For these, electrostatic forces are believed to contribute, including interactions between: side chains; the backbone and side chains; and side chains and the helix macrodipole. Here we probe these experimentally using designed peptides. We find that both terminal backbone-side chain and certain side chain-side chain interactions (i.e., local effects between proximal charges, or interatomic contacts) contribute much more to helix stability than side chain-helix macrodipole electrostatics, which are believed to operate at larger distances. This has implications for current descriptions of helix stability, understanding protein folding, and the refinement of force fields for biomolecular modelling and simulations. In addition, it sheds light on the stability of rod-like structures formed by single α-helices that are common in natural proteins including non-muscle myosins

CASSCF Computational Study of Pseudopericyclic Character in Electrocyclic Rearrangements Involving Heteroatoms

The Complete Active Space Self-Consistent Field (CASSCF) computational method, with the 6-31G* basis set, was used to examine six electrocyclic rearrangements, each involving a 1,2,4,6-heptatetraene skeleton with two variously located oxygen and/or nitrogen heteroatoms, as a way to determine which, if any, are pseudopericyclic as opposed to pericyclic. Primarily through the close examination of the active space orbitals, but also considering transition structure geometries and activation energies, it was concluded that rearrangements <b>3</b> → <b>4</b>, <b>5</b> → <b>6</b>, <b>7</b> → <b>8</b>, and <b>9</b> → <b>10</b> are pseudopericyclic with two orbital disconnections each, whereas the <b>13</b> → <b>14</b> and <b>15</b> → <b>16</b> rearrangements are pericyclic. Our conclusions agreed with those of others in two of the four cases that had been studied previously by density functional theory (<b>3</b> → <b>4</b> and <b>7</b> → <b>8</b>) but ran contrary to the previous conclusions that the <b>5</b> → <b>6</b> rearrangement is pericyclic and that the <b>15</b> → <b>16</b> rearrangement is pseudopericyclic. Our results are also compared and contrasted to previous similar ones of ours involving the <b>3</b> → <b>4</b> electrocyclization (essentially pericyclic), the <b>11</b> → <b>12</b> [3,3] sigmatropic rearrangement (pseudopericyclic), and similar [3,3] sigmatropic rearrangements (all pericyclic), and detailed rationales for these latest results are provided