ranging from 0.4 to 23 mM. The other class of molecules are halogenated cisimidazoline analogs such as Nutlin-3a that inhibit MDM2 with IC50 values ranging from 0.086 to 26 mM. To study the thermodynamics and kinetics of binding for these inhibitors, we build multi-ensemble Markov models (MEMMs) from explicit-solvent molecular dynamics trajectories of the binding/unbinding reactions biased by umbrella sampling (US) and scaled nonbonded interactions. This methodology allows us to observe significantly more binding and unbinding events than would be observed with unbiased sampling. We discuss the accuracy of estimated affinities and binding kinetics.
A groundbreaking work in 1970 by Arthur Ashkin paved the way for developing various optical trapping techniques. Optical tweezers have become an established method for the manipulation of biological objects, due to their noninvasiveness and precise controllability. Recent innovations are accelerating and now enable single-cell manipulation through holographic light structuring. In this review, we provide an overview of recent advances in optical tweezer techniques for studies at the individual cell level. Our review focuses on holographic optical tweezers that utilize active spatial light modulators to noninvasively manipulate live cells. The versatility of the technology has led to valuable integrations with microscopy, microfluidics, and biotechnological techniques for various single-cell studies. We aim to recapitulate the basic principles of holographic optical tweezers, highlight trends in their biophysical applications, and discuss challenges and future prospects.
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