Mixtures of dipolar and active colloidal particles display a variety of states including chains, string-fluids, and motility induced phase separation.

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Directing the assembly of colloidal particles through the use of external electric or magnetic fields shows promise for the creation of reconfigurable materials. Self-propelled particles can also be used to dynamically drive colloidal systems to nonequilibrium steady states. We investigate colloidal systems that combine both of these methods of directed assembly, simulating mixtures of passive dipolar colloids and active soft spheres in an external magnetic field using Brownian dynamics in two dimensions. In these systems, the dipolar particles align in the direction of the external field, but the active particles are unaffected by the field. The phase behaviors exhibited included a percolated dipolar network, dipolar string-fluid, isotropic fluid, and phase-separated state. We find that the external field allows the dipolar particles to form a percolated network more easily compared to when no external field is present. Additionally, the mixture phase separates at lower active particle velocity in an external field than when no field is present. Our results suggest that combining multiple methods of directing colloidal assembly could lead to new pathways to fabricate reconfigurable materials.

We decipher an atomic-level mechanism of Raf activation through dimerization, revealing that the disruption of intramolecular π–π stacking at the dimer interface promotes the OFF-to-ON transition.

The anchorage of Ras isoforms in the membrane and their nanocluster formations have been studied extensively, including their detailed interactions, sizes, preferred membrane environments, chemistry, and geometry. However, the staggering challenge of their epigenetics and chromatin accessibility in distinct cell states and types, which we propose is a major factor determining their specific expression, still awaits unraveling. Ras isoforms are distinguished by their C-terminal hypervariable region (HVR) which acts in intracellular transport, regulation, and membrane anchorage. Here, we review some isoform-specific activities at the plasma membrane from a structural dynamic standpoint. Inspired by physics and chemistry, we recognize that understanding functional specificity requires insight into how biomolecules can organize themselves in different cellular environments. Within this framework, we suggest that isoform-specific expression may largely be controlled by the chromatin density and physical compaction, which allow (or curb) access to “chromatinized DNA.” Genes are preferentially expressed in tissues: proteins expressed in pancreatic cells may not be equally expressed in lung cells. It is the rule—not an exception, and it can be at least partly understood in terms of chromatin organization and accessibility state. Genes are expressed when they can be sufficiently exposed to the transcription machinery, and they are less so when they are persistently buried in dense chromatin. Notably, chromatin accessibility can similarly determine expression of drug resistance genes.

Precision oncology benefits from effective early phase drug discovery decisions. Recently, drugging inactive protein conformations has shown impressive successes, raising the cardinal questions of which targets can profit and what are the principles of the active/inactive protein pharmacology. Cancer driver mutations have been established to mimic the protein activation mechanism. We suggest that the decision whether to target an inactive (or active) conformation should largely rest on the protein mechanism of activation. We next discuss the recent identification of double (multiple) same‐allele driver mutations and their impact on cell proliferation and suggest that like single driver mutations, double drivers also mimic the mechanism of activation. We further suggest that the structural perturbations of double (multiple) in cis mutations may reveal new surfaces/pockets for drug design. Finally, we underscore the preeminent role of the cellular network which is deregulated in cancer. Our structure‐based review and outlook updates the traditional Mechanism of Action, informs decisions, and calls attention to the intrinsic activation mechanism of the target protein and the rewired tumor‐specific network, ushering innovative considerations in precision medicine.

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