Anthony Nicholls

..Practical methods will be discussed, deeper issues in applying standard approaches addressed and research on successes and failures in other disciplines presented by invited experts...

..In doing so it is hard to be optimistic for the future of the field unless a greater commitment is made to basic science...

..Here we propose a modest beginning, with recommendations for requirements on statistical reporting, requirements for data sharing, and best practices for benchmark preparation and usage...

....

..We cannot know what new application to the design and discovery of pharmaceuticals may yet arise from the simple concept of molecular shape, but it is fair to say that the progress so far is impressive...

..Taken together these suggest the modeling field has a long way to go to provide effective assessment of its approaches, either to itself or to a broader audience, but that there are no technical reasons why progress cannot be made...

..6 kcal/mol, with the explicit solvent free energy approach yielding somewhat greater accuracy but at greater computational expense. Insights from outliers and suggestions for future prospective challenges of this kind are presented...

....

..It is shown that increasing levels of gas phase geometry optimization yield increasingly unfavorable solvation energy for single conformer models...

....

..This implies that this scoring function is not limited to more accurate x-ray structures, as is the case for many of the conventional docking methods, but could be extended to homology models...

..The results of this blind assessment of the state of the field for transfer energy and tautomer ratio prediction both indicate where the field is performing well and point out flaws in current methods...

..The results strongly suggest the need for new and repeated experimental measurements, both to clarify what appears to be experimental discrepancies in older measurements and to advance the field in a statistically sound manner...

..The results show that a shape-based, ligand-centric approach is more consistent than, and often superior to, the protein-centric approach taken by docking...

..We provide methods and evidence to support the conclusion that a useful encoding is practical and propose tests for falsification...

....

....

..This process resulted in Iridium, a highly trustworthy protein-ligand structure database to be used for development and validation of structure-based design tools for drug discovery...

..I present here some basic approaches that have proved useful in my own work, along with examples drawn from the field. In particular, the statistics of evaluations of virtual screening are carefully considered...

..Additionally, we show an effective methodology using the variables in hypothesis generation; namely, when the crystal structure of a bound ligand is not known...

..These experimental results validate this use of ROCS for chemotype switching or "lead hopping" and suggest that it is of general interest for lead identification in drug discovery endeavors...

..The accuracy of LINGO is demonstrated to be comparable to that of a path-based fingerprint and offers a simple yet effective method for similarity searching...