István Kolossváry

Publications (5)35.14 Total impact

• Article: A twist on folding: Predicting optimal sequences and optimal folds of simple protein models with the hidden-force algorithm

  István Kolossváry, Kevin J. Bowers
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  ABSTRACT: We propose a new way of looking at global optimization of off-lattice protein models. We present a dual optimization concept of predicting optimal sequences as well as optimal folds. We validate the utility of the recently introduced hidden-force Monte Carlo optimization algorithm by finding significantly lower energy folds for minimalist protein models than previously reported. Further, we also find the protein sequence that yields the lowest energy fold amongst all sequences for a given chain length and residue mixture. In particular, for protein models with a binary sequence, we show that the sequence-optimized folds form more compact cores than the lowest energy folds of the historically fixed, Fibonacci-series sequences of chain lengths of 13, 21, 34, 55, and 89. We emphasize that while the protein model we used is minimalist, the methodology is applicable to detailed protein models, and sequence optimization may yield novel folds and aid de novo protein design.
  05/2012;
• Article: Global optimization of additive potential energy functions: predicting binary Lennard-Jones clusters.

  István Kolossváry, Kevin J Bowers
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  ABSTRACT: We present a method for minimizing additive potential-energy functions. Our hidden-force algorithm can be described as an intricate multiplayer tug-of-war game in which teams try to break an impasse by randomly assigning some players to drop their ropes while the others are still tugging until a partial impasse is reached, then, instructing the dropouts to resume tugging, for all teams to come to a new overall impasse. Utilizing our algorithm in a non-Markovian parallel Monte Carlo search, we found 17 new putative global minima for binary Lennard-Jones clusters in the size range of 90-100 particles. The method is efficient enough that an unbiased search was possible; no potential-energy surface symmetries were exploited. All new minima are comprised of three nested polyicosahedral or polytetrahedral shells when viewed as a nested set of Connolly surfaces (though the shell structure has previously gone unscrutinized, known minima are often qualitatively similar). Unlike known minima, in which the outer and inner shells are comprised of the larger and smaller atoms, respectively, in 13 of the new minima, the atoms are not as clearly separated by size. Furthermore, while some known minima have inner shells stabilized by larger atoms, four of the new minima have outer shells stabilized by smaller atoms.
  Physical Review E 11/2010; 82(5 Pt 2):056711. · 2.26 Impact Factor
• Source

  Available from: Ravenna Flitman-Tene

  Article: Mechanism of Na+/H+ antiporting.

  Isaiah T Arkin, Huafeng Xu, Morten Ø Jensen, Eyal Arbely, Estelle R Bennett, Kevin J Bowers, Edmond Chow, Ron O Dror, Michael P Eastwood, Ravenna Flitman-Tene, Brent A Gregersen, John L Klepeis, István Kolossváry, Yibing Shan, David E Shaw
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  ABSTRACT: Na+/H+ antiporters are central to cellular salt and pH homeostasis. The structure of Escherichia coli NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp164 (D164) is the Na+-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na+ ion: D163 protonates to reveal the Na+-binding site to the periplasm, and subsequent protonation of D164 releases Na+. Additional mutagenesis experiments further validated the model.
  Science 09/2007; 317(5839):799-803. · 31.20 Impact Factor
• Source

  Available from: Huafeng Xu

  Conference Proceeding: Molecular dynamics - Scalable algorithms for molecular dynamics simulations on commodity clusters.

  Kevin J. Bowers, Edmond Chow, Huafeng Xu, Ron O. Dror, Michael P. Eastwood, Brent A. Gregersen, John L. Klepeis, István Kolossváry, Mark A. Moraes, Federico D. Sacerdoti, John K. Salmon, Yibing Shan, David E. Shaw
  Proceedings of the ACM/IEEE SC2006 Conference on High Performance Networking and Computing, November 11-17, 2006, Tampa, FL, USA; 01/2006
• Article: Molecular dynamics simulation of cyclodextrin inclusion complexes in enzymatic lipid hydrolysis

  Györgyi J. Kolossváry, István Kolossváry
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  ABSTRACT: Cyclodextrin derivatives can increase the enzymatic hydrolysis of triolein in aqueous solution. Two types of cyclodextrin inclusion complexes could be responsible for this effect. In the present study, molecular dynamics simulations clearly suggest that cyclodextrin hosts only the liberated fatty acid thus accelerating lipolysis by decreasing product inhibition.
  Biotechnology Letters 03/1996; 18(4):440-444. · 1.68 Impact Factor