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PROTDES: CHARMM toolbox for computational protein design.

Suárez M, Tortosa P, Jaramillo A - Syst Synth Biol (2009)

Bottom Line: PROTDES allows the integration of molecular dynamics within the protein design.Our software allows CHARMM users to perform protein design calculations and to create their own procedures for protein design using their own energy functions.We show this by implementing three different energy functions based on different solvent treatments: surface area accessibility, generalized Born using molecular volume and an effective energy function.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Laboratory, CNRS-UMR 7654, Ecole Polytechnique, 91128, Palaiseau, France, Maria.Suarez@polytechnique.edu.

ABSTRACT
We present an open-source software able to automatically mutate any residue positions and find the best aminoacids in an arbitrary protein structure without requiring pairwise approximations. Our software, PROTDES, is based on CHARMM and it searches automatically for mutations optimizing a protein folding free energy. PROTDES allows the integration of molecular dynamics within the protein design. We have implemented an heuristic optimization algorithm that iteratively searches the best aminoacids and their conformations for an arbitrary set of positions within a structure. Our software allows CHARMM users to perform protein design calculations and to create their own procedures for protein design using their own energy functions. We show this by implementing three different energy functions based on different solvent treatments: surface area accessibility, generalized Born using molecular volume and an effective energy function. PROTDES, a tutorial, parameter sets, configuration tools and examples are freely available at http://soft.synth-bio.org/protdes.html .

No MeSH data available.


Structure of the mutated DNA interacting with the mutated cI repressor protein: the DNA mutations A4C, (chain LMBA) and T38G (chain LMBB) and the cI protein mutation Q44I have change the protein DNA interaction
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Fig5: Structure of the mutated DNA interacting with the mutated cI repressor protein: the DNA mutations A4C, (chain LMBA) and T38G (chain LMBB) and the cI protein mutation Q44I have change the protein DNA interaction

Mentions: Due to the low number of positions to design we have utilized the exhaustive procedure in the optimization so that all the rotamers in library will be patched in each iteration, we found that even with 5 heuristic iteration convergence was achieved, the results of 5 out of 10 runnings, corresponding to the minimal energy found was identical. Increasing the number of steps provided the same results. PROTDES proposed the Q44I mutation, that together with the side chain modeling of Q33 managed to lower the energy of the complex by 3.2 kcal/mol. The interactions with DNA have also changed, now its backbone is involved as can be seen in Fig. 5.Fig. 5


PROTDES: CHARMM toolbox for computational protein design.

Suárez M, Tortosa P, Jaramillo A - Syst Synth Biol (2009)

Structure of the mutated DNA interacting with the mutated cI repressor protein: the DNA mutations A4C, (chain LMBA) and T38G (chain LMBB) and the cI protein mutation Q44I have change the protein DNA interaction
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2735645&req=5

Fig5: Structure of the mutated DNA interacting with the mutated cI repressor protein: the DNA mutations A4C, (chain LMBA) and T38G (chain LMBB) and the cI protein mutation Q44I have change the protein DNA interaction
Mentions: Due to the low number of positions to design we have utilized the exhaustive procedure in the optimization so that all the rotamers in library will be patched in each iteration, we found that even with 5 heuristic iteration convergence was achieved, the results of 5 out of 10 runnings, corresponding to the minimal energy found was identical. Increasing the number of steps provided the same results. PROTDES proposed the Q44I mutation, that together with the side chain modeling of Q33 managed to lower the energy of the complex by 3.2 kcal/mol. The interactions with DNA have also changed, now its backbone is involved as can be seen in Fig. 5.Fig. 5

Bottom Line: PROTDES allows the integration of molecular dynamics within the protein design.Our software allows CHARMM users to perform protein design calculations and to create their own procedures for protein design using their own energy functions.We show this by implementing three different energy functions based on different solvent treatments: surface area accessibility, generalized Born using molecular volume and an effective energy function.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Laboratory, CNRS-UMR 7654, Ecole Polytechnique, 91128, Palaiseau, France, Maria.Suarez@polytechnique.edu.

ABSTRACT
We present an open-source software able to automatically mutate any residue positions and find the best aminoacids in an arbitrary protein structure without requiring pairwise approximations. Our software, PROTDES, is based on CHARMM and it searches automatically for mutations optimizing a protein folding free energy. PROTDES allows the integration of molecular dynamics within the protein design. We have implemented an heuristic optimization algorithm that iteratively searches the best aminoacids and their conformations for an arbitrary set of positions within a structure. Our software allows CHARMM users to perform protein design calculations and to create their own procedures for protein design using their own energy functions. We show this by implementing three different energy functions based on different solvent treatments: surface area accessibility, generalized Born using molecular volume and an effective energy function. PROTDES, a tutorial, parameter sets, configuration tools and examples are freely available at http://soft.synth-bio.org/protdes.html .

No MeSH data available.