The Top Ten Challenges

1 IN SILICO SCREENING OF DRUG COMPOUNDS would be a major achievement. The ability to predict the efficacy and side effects of lead compounds using computer modeling and simulation would also reduce the need for risky human testing and would save significant amounts of money and time that are now spent in the laboratory. The core of this improvement would be computation of affinities of lead compounds to targets and to effectors of potential side effects.

2 PREDICTING FUNCTION FROM STRUCTURE OF COMPLEX MOLECULES at an engineering level of precision is not now possible. Currently, molecular simulation and analysis methods capture the essence of the mechanism of biomolecular function, but do not predict that function with quantitative accuracy. Improved capability in this regard would lead to a precise understanding of the consequences of mutations and other biological variations, and the ability to design molecules for medical nanotechnology.

3 PREDICTION OF PROTEIN STRUCTURE to the point where all protein sequences have associated accurate structures would provide critically important information. At present there are many more known protein sequences than structures. By a combination of accelerated experimental structure determination and improved techniques for mining known structures to determine the rules for predicting unknown structures, it should be possible to fill in the gaps and assign a structure to every sequence. Success in this arena would advance the field of biomedicine in many and various ways.