Protein structure prediction is considered as one of the most challenging and computationally int... more Protein structure prediction is considered as one of the most challenging and computationally intractable combinatorial problem. Thus, the efficient modeling of convoluted search space, the clever use of energy functions, and more importantly, the use of effective sampling algorithms become crucial to address this problem. For protein structure modeling, an off-lattice model provides limited scopes to exercise and evaluate the algorithmic developments due to its astronomically large set of data-points. In contrast, an on-lattice model widens the scopes and permits studying the relatively larger proteins because of its finite set of data-points. In this work, we took the full advantage of an on-lattice model by using a face-centered-cube lattice that has the highest packing density with the maximum degree of freedom. We proposed a graded energy-strategically mixes the Miyazawa-Jernigan (MJ) energy with the hydrophobic-polar (HP) energy-based genetic algorithm (GA) for conformational ...
Proceedings of the 6th International Conference on Foundations of Digital Games - FDG '11, 2011
ABSTRACT As games grow in complexity, gameplay needs to provide players with powerful means of ma... more ABSTRACT As games grow in complexity, gameplay needs to provide players with powerful means of managing this complexity. One approach is to give automation tools to players. In this paper, we analyze an in-game automation tool, the Foldit cookbook, for the scientific ...
The protein structure prediction problem continues to elude scientists. Even though many new meth... more The protein structure prediction problem continues to elude scientists. Even though many new methods have been introduced, certain classes of prediction targets such as free modeling targets remain a challenge based on blind predictions in the several previous Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiments [1]. To meet this challenge, a large-scale collaborative effort called WeFold was undertaken by thirteen labs, each with their own specialties and approaches in addressing the problem. In this talk, we will present the different methods or branches collaboratively designed and tested during the WeFold experiment, as well as their predictive ability, outcomes, and lessons learned. Independent branches involved in the collaborative effort yielded several high-ranking predictions among all group and method submissions in CASP10 for human, free modeling (template free), and refinement targets. Remarkably, two WeFold methods were able to produce t...
Public participation in scientific research can be a powerful supplement to more-traditional appr... more Public participation in scientific research can be a powerful supplement to more-traditional approaches. We discuss aspects of the public participation project Foldit that may help others interested in starting their own projects.
Computational enzyme design holds promise for the production of renewable fuels, drugs and chemic... more Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems.
Protein structure prediction is considered as one of the most challenging and computationally int... more Protein structure prediction is considered as one of the most challenging and computationally intractable combinatorial problem. Thus, the efficient modeling of convoluted search space, the clever use of energy functions, and more importantly, the use of effective sampling algorithms become crucial to address this problem. For protein structure modeling, an off-lattice model provides limited scopes to exercise and evaluate the algorithmic developments due to its astronomically large set of data-points. In contrast, an on-lattice model widens the scopes and permits studying the relatively larger proteins because of its finite set of data-points. In this work, we took the full advantage of an on-lattice model by using a face-centered-cube lattice that has the highest packing density with the maximum degree of freedom. We proposed a graded energy-strategically mixes the Miyazawa-Jernigan (MJ) energy with the hydrophobic-polar (HP) energy-based genetic algorithm (GA) for conformational ...
Proceedings of the 6th International Conference on Foundations of Digital Games - FDG '11, 2011
ABSTRACT As games grow in complexity, gameplay needs to provide players with powerful means of ma... more ABSTRACT As games grow in complexity, gameplay needs to provide players with powerful means of managing this complexity. One approach is to give automation tools to players. In this paper, we analyze an in-game automation tool, the Foldit cookbook, for the scientific ...
The protein structure prediction problem continues to elude scientists. Even though many new meth... more The protein structure prediction problem continues to elude scientists. Even though many new methods have been introduced, certain classes of prediction targets such as free modeling targets remain a challenge based on blind predictions in the several previous Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiments [1]. To meet this challenge, a large-scale collaborative effort called WeFold was undertaken by thirteen labs, each with their own specialties and approaches in addressing the problem. In this talk, we will present the different methods or branches collaboratively designed and tested during the WeFold experiment, as well as their predictive ability, outcomes, and lessons learned. Independent branches involved in the collaborative effort yielded several high-ranking predictions among all group and method submissions in CASP10 for human, free modeling (template free), and refinement targets. Remarkably, two WeFold methods were able to produce t...
Public participation in scientific research can be a powerful supplement to more-traditional appr... more Public participation in scientific research can be a powerful supplement to more-traditional approaches. We discuss aspects of the public participation project Foldit that may help others interested in starting their own projects.
Computational enzyme design holds promise for the production of renewable fuels, drugs and chemic... more Computational enzyme design holds promise for the production of renewable fuels, drugs and chemicals. De novo enzyme design has generated catalysts for several reactions, but with lower catalytic efficiencies than naturally occurring enzymes. Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure. Players of the online game Foldit were challenged to remodel the backbone of a computationally designed bimolecular Diels-Alderase to enable additional interactions with substrates. Several iterations of design and characterization generated a 24-residue helix-turn-helix motif, including a 13-residue insertion, that increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems.
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Papers by Firas Khatib