Simulating Dilute-Solution Properties and Behavior of Flexible Macromolecules: A Review of Brownian Dynamics, Monte Carlo Methods, and Computational Tools (SIMUFLEX and MONTEHYDRO) with Applications to Biomacromolecules and Selected Synthetic Polymers.

Dilute-solution properties are important sources of information on the structure of macromolecules. Analyzing experimental data and extracting information on structural properties require theoretical and computational resources. The resources needed to study rigid particles are manageable; however, studying flexible particles is more challenging. This is because, unlike rigid bodies, and as a consequence of the conformational variability arising from flexibility, flexible particles do not have a definite size and shape. In addition to their overall translational and rotational Brownian motion, the dynamics of flexible particles in solution has an internal component: size/shape conformational fluctuations. In order to facilitate the study of flexible macromolecule hydrodynamics, we have implemented existing theories within several computer programs. MONTEHYDRO combines Monte Carlo simulations based on the importance-sampling algorithm to generate conformations from which, in addition to conformational quantities, the hydrodynamic properties of flexible particles can be obtained using rigid-body treatment. SIMUFLEX is a suite based on a Brownian dynamics simulation of macromolecules, comprising BROWFLEX, for the generation of trajectories, and ANAFLEX, for the calculation of static and time-dependent properties as well as the simulation of single-particle events. In this paper, we present some concepts which are fundamental to the methods implemented in those computational tools, as well as examples of their utilization in various biomacromolecule applications, with a particular emphasis on double-stranded DNA in various cases: coarse-grained double-helical models for moderately short DNA; the worm-like model treatment of DNA over an extremely wide range of sizes (from 8 to 200,000 base pairs); and the problem of the anomalous rotational-speed dependence of the sedimentation coefficient of very long DNA. SIMUFLEX has also been particularly useful for studying intrinsically partially disordered proteins, whose structure comprises both ordered, globular domains as well as flexible tail and linker chains. To illustrate applications in the field of synthetic polymers, we describe a study on dendrimers, with aspects related to drug delivery in targeted therapies.