Energy minimization Potential Energy, U(R Conformational Space, R X-ray structure Iterative procedures terminate when reach F=-VU(r) tolerance, such as small gradient M +I=r+sF Poor initial structure leads to poor local minimum Multiple minimum problem ONLY FINDS LOCAL MINIMA!Energy Minimization Conformational Space, R Potential Energy, U(R) X-ray structure X • Iterative procedures; terminate when reach tolerance, such as small F ( i = −∇ r U )i gradient • Poor initial structure leads ri+1 = ri + δ Fi to poor local minimum • Multiple minimum problem ONLY FINDS LOCAL MINIMA!