10 March 2000 Ž . Chemical Physics Letters 319 2000 65–70 www.elsevier.nlrlocatercplett Evaluation of the iterative simulated annealing technique in conformational search of peptides Francesc J. Corcho a , Marta Filizola b , Juan Jesus Perez a, ) ´ ´ a Dept. d’Enginyeria Quimica, UPC, ETS d’Enginyers Industrials de Barcelona. AÕ. Diagonal 647, 08028 Barcelona, Spain b ( ) Centro di Ricerca Interdipartimentale di Scienze Computazionali e Biotecnologiche CRISCEB , Seconda UniÕersita degli Studi di Napoli, ` Via Costantinopoli 16, 80138 Napoli, Italy Received 21 August 1999 Abstract Characterization of the subset of low energy minima of a peptide is hampered by the multiple minima problem associated to the roughness of its potential energy surface. The iterative simulated annealing procedure was recently proposed as an effective procedure to overcome these difficulties. In the present work results of a thorough exploration of the conforma- tional space of the peptide Ac–Cys–Val–Tic–Met performed by means of the simulated annealing procedure is compared to the results of a random search. Profile differences in the two sets of low energy conformations obtained are analyzed. The results are also discussed in terms of the rotational isomeric model and its usefulness in assessing the degree of completeness of the conformational search. q 2000 Elsevier Science B.V. All rights reserved. 1. Introduction Potential energy surfaces of peptides are charac- terized by the presence of a large number of valleys Ž . wx minima separated by high mountains and ridges 1 . The minima in the continuously defined potential energy surface, constitute a discrete set of mi- crostates called conformational substates. As a con- sequence the characterization of the subset of confor- mations that are thermodynamically or kinetically relevant and contribute to the description of the conformational profile of different peptides is ham- pered by the difficulties associated with a thorough exploration of the conformational space. This prob- ) Corresponding author. Fax: q 34-93-401-7150 lem is referred in the literature as the multiple min- ima problem and it is still an open question, despite the many techniques available to explore the confor- w x mational space of peptides 2,3 . Some insights into the features of the conforma- tional space can be assessed from the study of the density of states profile of such systems. From the few thorough explorations of the conformational space of different flexible molecules published in the w x past 4–9 , it can be deduced that the histogram representing the number of conformations rank or- dered by energy of such systems, exhibits a bimodal distribution. More specifically, for conformations with energy close to the global minimum, the distri- bution exhibits a characteristic exponential growth reaching two maxima at energies relative to the 0009-2614r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. Ž . PII: S0009-2614 00 00081-6