Geometry optimization and transition state search in enzymes: Different options in the microiterative method

Xavier Prat-Resina, Josep Maria Bofill, Àngels González-Lafont, José M. Lluch

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


In the current article we present a systematic analysis of the different options in the so-called "microiterative method" used to locate minima and transitionstate (TS) structures of big systems on quantum mechanics/molecular mechanics potential energy surfaces. The method splits the system in two parts: a core zone in which accurate second-order search is carried out, and an environment that is kept minimized with a cheap first-order algorithm. The different options studied here are: the alternating frequency between the environment minimization and the TS search in the core, the number of atoms included in each zone, and two alternative ways to reduce the computational cost in the calculation of core-environment interactions. The tests have been done at two different steps of the enzymatic mechanism of mandelate racemase: a proton transfer and a carbon configuration inversion step. The two selected TS structures differ in the number of atoms involved in their associated transition vectors; the proton transfer TS is an example of a local motion, whereas the carbon configuration inversion TS corresponds to a more global movement of several groups and residues, including an important number of atoms.

Original languageEnglish (US)
Pages (from-to)367-377
Number of pages11
JournalInternational Journal of Quantum Chemistry
Issue number4
StatePublished - Jun 15 2004
Externally publishedYes


  • Enzyme catalysis
  • Mandelate Racemase reaction mechanisms
  • Microiterative method
  • QM/MM transition state structures
  • Second derivatives direct optimization method


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