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Molecular Simulation


The Molecular Simulation Laboratory develops and applies theoretical/computational methods to study the atomic-level determinants of the behavior of (bio)molecules. 


António M. Baptista
Investigador Auxiliar
PhD in 1998, UNL, Portugal

Phone (+351) 214469619
Extension 1619



Research Interests

The Molecular Simulation Laboratory puts a strong emphasis on developing novel biomolecule-oriented methods derived from physical principles, particularly Statistical Thermodynamics. This allows us to study biological processes that are difficult or impossible to address using standard methodologies. A major line of work deriving from such developments is the inclusion in simulation methods of experimentally important parameters that are essentially electrostatic, such as the pH, ionic strength and reduction potential of the solution. This made possible the detailed study of the structural changes induced by pH and/or reduction potential on several peptides and proteins, such as kyotorphin (an analgesic neuropeptide), polylysine (a polymer displaying a helix-coil transition) and cytochrome c3 (an enzyme that breaks the walls of Gram-positive bacteria). A major extension to address biological membranes and nonequilibrium conditions is currently being undertaken.

Another research subject is the study of peptide and protein folding/misfolding and the characterization of their energy landscapes, a kind of topographic map displaying the conformational preferences of the molecule. We started by performing a critical study of energy landscapes in a decapeptide, identifying some problems of the usual approaches and proposing a robust method to identify conformation classes. We are presently studying the prion protein, which is associated with the Creutzfeldt-Jakob disease and other amyloid diseases, and whose misfolding is thought to be caused in vivo by the low pH of endosomes. Our study observed that pH decrease induces the loss of helical structure and gain of new beta-structure, in agreement with experiments, identifying the regions where those changes take place. This approach will be applied to other cases of pH-induced misfolding.

A recent research line in our laboratory is the structural characterization of peptide dendrimers, tree-like synthetic molecules formed by alternating functional amino acids with branching diamino acids. There is a large variety of applications for peptide dendrimers, including in the area of biomedicine, but the understanding of their structure/function relationship has so far been hindered by the inability to experimentally determine their structures. We are currently investigating the conformational preferences of several dendrimers, including those mimicking the cobalamin binding of B12-dependent enzymes.


Group Members

    • Miguel Machuqueiro, Post Doc
    • Sara Campos, PhD student


Selected Publications

  1. Machuqueiro, M., Baptista, A. M. (2007) "The pH-dependent conformational states of kyotorphin: a constant-pH molecular dynamics study." Biophysics Journal 92(6):1836-1845.
  2. Machuqueiro, M., Baptista, A. M. (2009) "Molecular dynamics at constant pH and reduction potential: application to cytochrome c3." Journal of the American Chemical Society 131(35):12586-12594.
  3. Campos, S. R. R., Baptista, A. M. (2009) "Conformational analysis in a multidimensional energy landscape: study of an arginylglutamate repeat." Journal of Physical Chemistry B 113(49):15989-16001. 

Laboratory's Website

For further information please visit the laboratory's website


Simulação Molecular (PT)

O Laboratório de Simulação Molecular estuda o funcionamento das moléculas usando métodos computacionais. Esses métodos baseiam-se nas leis físicas que governam os átomos e moléculas, permitindo simular o seu comportamento. Tais simulações tornam possível investigar processos cujo estudo experimental é difícil, demorado, ou mesmo impossível. Assim, por exemplo, se quisermos entender a nível molecular de que modo uma proteína realiza a sua tarefa no nosso organismo, a simulação pode dar-nos pistas sobre quais as partes da proteína directamente envolvidas nessa tarefa, bem como as consequências da modificação dessas partes. Uma das principais linhas de trabalho do Laboratório de Simulação Molecular é o desenvolvimento de métodos computacionais para estudar o efeito do pH no comportamento das moléculas. Esses e outros métodos são depois usados para entender as bases moleculares de vários processos de interesse biológico, médico ou tecnológico.


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