59,580 research outputs found
Inverse Quantum Chemistry: Concepts and Strategies for Rational Compound Design
The rational design of molecules and materials is becoming more and more
important. With the advent of powerful computer systems and sophisticated
algorithms, quantum chemistry plays an important role in rational design. While
traditional quantum chemical approaches predict the properties of a predefined
molecular structure, the goal of inverse quantum chemistry is to find a
structure featuring one or more desired properties. Herein, we review inverse
quantum chemical approaches proposed so far and discuss their advantages as
well as their weaknesses.Comment: 43 pages, 5 figure
Gradient-Driven Molecule Construction: An Inverse Approach Applied to the Design of Small-Molecule Fixating Catalysts
Rational design of molecules and materials usually requires extensive
screening of molecular structures for the desired property. The inverse
approach to deduce a structure for a predefined property would be highly
desirable, but is, unfortunately, not well-defined. However, feasible
strategies for such an inverse design process may be successfully developed for
specific purposes. We discuss options for calculating 'jacket' potentials that
fulfill a predefined target requirement - a concept that we recently introduced
[T. Weymuth, M. Reiher, MRS Proceediungs, 2013, 1524,
DOI:10.1557/opl.2012.1764]. We consider the case of small-molecule activating
transition metal catalysts. As a target requirement we choose the vanishing
geometry gradients on all atoms of a subsystem consisting of a metal center
binding the small molecule to be activated. The jacket potential can be
represented within a full quantum model or by a sequence of approximations of
which a field of electrostatic point charges is the simplest. In a second step,
the jacket potential needs to be replaced by a chemically viable chelate-ligand
structure for which the geometry gradients on all of its atoms are also
required to vanish. In order to analyze the feasibility of this approach, we
dissect a known dinitrogen-fixating catalyst to study possible design
strategies that must eventually produce the known catalyst.Comment: 40 pages, 6 tables, 5 figure
Protein Docking by the Underestimation of Free Energy Funnels in the Space of Encounter Complexes
Similarly to protein folding, the association of two proteins is driven
by a free energy funnel, determined by favorable interactions in some neighborhood of the
native state. We describe a docking method based on stochastic global minimization of
funnel-shaped energy functions in the space of rigid body motions (SE(3)) while accounting
for flexibility of the interface side chains. The method, called semi-definite
programming-based underestimation (SDU), employs a general quadratic function to
underestimate a set of local energy minima and uses the resulting underestimator to bias
further sampling. While SDU effectively minimizes functions with funnel-shaped basins, its
application to docking in the rotational and translational space SE(3) is not
straightforward due to the geometry of that space. We introduce a strategy that uses
separate independent variables for side-chain optimization, center-to-center distance of the
two proteins, and five angular descriptors of the relative orientations of the molecules.
The removal of the center-to-center distance turns out to vastly improve the efficiency of
the search, because the five-dimensional space now exhibits a well-behaved energy surface
suitable for underestimation. This algorithm explores the free energy surface spanned by
encounter complexes that correspond to local free energy minima and shows similarity to the
model of macromolecular association that proceeds through a series of collisions. Results
for standard protein docking benchmarks establish that in this space the free energy
landscape is a funnel in a reasonably broad neighborhood of the native state and that the
SDU strategy can generate docking predictions with less than 5 ļæ½ ligand interface Ca
root-mean-square deviation while achieving an approximately 20-fold efficiency gain compared
to Monte Carlo methods
Multiconfigurational Short-Range Density-Functional Theory for Open-Shell Systems
Many chemical systems cannot be described by quantum chemistry methods based
on a singlereference wave function. Accurate predictions of energetic and
spectroscopic properties require a delicate balance between describing the most
important configurations (static correlation) and obtaining dynamical
correlation efficiently. The former is most naturally done through a
multiconfigurational (MC) wave function, whereas the latter can be done by,
e.g., perturbation theory. We have employed a different strategy, namely, a
hybrid between multiconfigurational wave functions and density-functional
theory (DFT) based on range separation. The method is denoted by MC short-range
(sr) DFT and is more efficient than perturbative approaches as it capitalizes
on the efficient treatment of the (short-range) dynamical correlation by DFT
approximations. In turn, the method also improves DFT with standard
approximations through the ability of multiconfigurational wave functions to
recover large parts of the static correlation. Until now, our implementation
was restricted to closed-shell systems, and to lift this restriction, we
present here the generalization of MC-srDFT to open-shell cases. The additional
terms required to treat open-shell systems are derived and implemented in the
DALTON program. This new method for open-shell systems is illustrated on
dioxygen and [Fe(H2O)6]3+.Comment: 37 pages, 3 figures, 4 tables, 1 appendix and 79 references Changes
in v2: 1) Appendix B and reference 81 removed 2) Removed dublicated reference
and corrected reference 31. 3) Added spin-charge cross terms to GGA (Appendix
A). Code changed accordingly and GGA results recalculated. All GGA results
are revised -only small modifications observed. Conclusions are unchange
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