Untitled

Abstract

The three-dimensional spatial structure of a methylene-acetal-linked thymine dimer present in a 10 basepair (bp) sense-antisense DNA duplex was studied with a genetic algorithm designed to interpret NOE distance restraints. Trial solutions were represented by torsion angles. This means that bond angles for the dimer trial structures are kept fixed during the genetic algorithm optimization. Bond angle values were extracted from a 10 bp sense-antisense duplex model that was subjected to energy minimization by means of a modified AMBER force field. A set of 63 proton-proton distance restraints defining the methylene-acetal-linked thymine dimer was available. The genetic algorithm minimizes the difference between distances in the trial structures and distance restraints. A large conformational search space could be covered in the genetic algorithm optimization by allowing a wide range of torsion angles. The genetic algorithm optimization in all cases led to one family of structures. This family of the methylene-acetal-linked thymine dimer in the duplex differs from the family that was suggested from distance geometry calculations. It is demonstrated that the bond angle geometry around the methylene-acetal linkage plays an important role in the optimization.

A Test of the Single-Conformation Hypothesis in the Analysis of NMR Data for Small Polar Molecules: A Force Field Comparison

“…Other approaches for deconvoluting dynamic NMR averages include genetic algorithms, , MEDUSA, , CPA, PEPFLEX-II, and NAMFIS . Genetic algorithms have been used to generate conformations that are consistent with solution NOE distance information …”

“…22 Genetic algorithms have been used to generate conformations that are consistent with solution NOE distance information. 16 MEDUSA and CPA produce clusters of conformations that likewise represent conformational space by utilizing NOE distance constraints. PEPFLEX-II and NAMFIS operate on structures from a conformational search generated independently of NMR data (e.g., from a force field only).…”

Efficient and Unbiased Sampling of Biomolecular Systems in the Canonical Ensemble: A Review of Self‐Guided Langevin Dynamics

“…By contrast, there is a wide variety of build-up (Budin et al 2001) and construction methods that make use of libraries (Kolossvary & Guida 1999; Loferer et al 2007; McMartin & Bohacek 1997; Spellmeyer et al 1997), genetic algorithms (Beckers et al 1997; Dandekar & Argos 1992; Jones et al 1997; Le Grand & Merz 1994; Ogata et al 1995), or exhaustive enumeration (Brower et al 1993; Brown et al 2005; Duan & Kollman 2001; Faulon et al 2003). There are also combined methods, such as the conformation space annealing (CSA) (Lee et al 1999a; Lee et al 1999b) method which uses multiple techniques to generate an extensive variety of widely separated conformations.…”

Non‐uniform sampling for NOESY? A case study on spiramycin

“…Accordingly, as most (small) molecules of real-life relevance are flexible, the experimentally observed NOEs are typically the population-weighted averages of the NOEs of their conformers and do not represent a single geometry. [15] A number of algorithms, such as MEDUSA, [16] CPA, [17] PEPFLEX-II, [18] FINGAR, [19] DISCON, [20] NAMFIS, [21] GENFOLD [22] and StereoFitter, [23] have been developed to deconvolute the population-averaged NOE data into the interatomic distances of a set of conformations with their corresponding molar fractions, taking the distance dependency of the NOE intensity into consideration. Despite being readily available, these are not yet extensively used by non-experts.…”